Antibacterial agents

Abstract

Antibacterial compounds of formula I are provided: 1

Description

[0001] This application claims benefit of priority to the following U.S. Provisional Patent Applications, serial No. 60/438,523, filed Jan. 8, 2003; serial No. 60/466,974, filed Apr. 30, 2003; and serial No. 60/520,211 filed Nov. 13, 2003; each of which is incorporated herein by reference in its entirety for any purpose.

FIELD OF THE INVENTION

[0002] This invention pertains generally to treating infections caused by gram-negative bacteria. More specifically, the invention described herein pertains to treating gram-negative infections by inhibiting activity of UDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC). The present invention provides small molecule inhibitors of LpxC, pharmaceutical formulations containing such inhibitors, methods of treating patients with such pharmaceutical formulations, and to methods of preparing such pharmaceutical formulations and inhibitors. The inhibitors can be used to treat Gram-negative infections of patients alone and in combination with other antibacterials.

BACKGROUND OF THE INVENTION

[0003] Over the past several decades, the frequency of antimicrobial resistance and its association with serious infectious diseases have increased at alarming rates. The increasing prevalence of resistance among nosocomial pathogens is particularly disconcerting. Of the over 2 million nosocomial infections occuriing each year in the United States, 50 to 60% are caused by antimicrobial-resistant strains of bacteria. This, high rate of resistance increases the morbidity, mortality, and costs associated with nosocomial infections. In the United States, nosocomial infections are thought to contribute to or cause more than 77,000 deaths per year and cost approximately $5 to $10 billion annually. Among Gram-positive organisms, the most important resistant pathogens are methicillin-(oxacillin-)resistant Staphylococcus aureus, &bgr;-lactam-resistant and multidrug-resistant pneumococci, and vancomycin-resistant enterococci. Important causes of Gram-negative resistance include extended-spectrum &bgr;-lactamases (ESBLs) in Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis, high-level third-generation cephalosporin (Amp C) &bgr;-lactamase resistance among Enterobacter species and Citrobacter freundii, and multidrug-resistance genes observed in Pseudomonas aeruginosa, Acinetobacter, and Stenotrophomonas maltophilia. (Jones RN 2001 Chest 119 (supplement), 397S-404S: Resistance patterns among nosocomial pathogens: Trends over the past few years.)

[0004] The problem of antibacterial resistance is compounded by the existence of bacterial strains resistant to multiple antibacterials. For example, Pseudomonas aeruginosa isolates resistant to fluoroquinolones are virtually all resistant to additional antibacterials (Sahm DF et al 2001 Antimicrobial Agents and Chemotherapy 45, 267-274: Evaluation of current activities of fluoroquinolones against gram-negative bacilli using centralized in vitro testing and electronic surveillance.)

[0005] Thus there is a need for new antibacterials, particularly antibacterials with novel mechanisms of action. Most of the antibacterial discovery effort in the pharmaceutical industry is aimed at development of drugs effective against gram-positive bacteria. However, there is also a need for new gram-negative antibacterials. Gram-negative bacteria are in general more resistant to a large number of antibacterials and chemotherapeutic agents than are gram-positive bacteria. A survey of recently reported antibacterials of natural origin showed that over 90% lacked activity against Escherichia coli, although they were active against gram-positive bacteria. The outer membrane of gram-negative bacteria contributes to this intrinsic resistance by acting as an efficient permeability barrier, because the narrow porin channels limit the penetration of hydrophilic solutes and the low fluidity of the lipopolysaccharide leaflet slows down the inward diffusion of lipophilic solutes. A second mechanism contributes to the intrinsic resistance of gram-negative bacteria. Recent studies showed that multiple drug efflux pumps, sometimes with unusually broad specificity, act as this second factor to create the general intrinsic resistance of gram-negative bacteria. When their expression levels are elevated as a consequence of physiological regulation or genetic alteration, they can frequently produce impressive levels of resistance to a wide variety of antimicrobial agents. (Nikaido H 1998 Clinical Infectious Diseases 27(Suppl 1), S32-41: Antibacterial resistance caused by gram-negative multidrug efflux pumps.)

[0006] Historically, most development of antimicrobial agents has been relatively empirical. Active compounds have generally been found via screening soil, sewage, water, and other natural substances to detect antimicrobial-producing organisms, or by screening various chemical compounds. Once a leading candidate has been found and its chemical structure determined, a series of analogs is made to identify an optimal compound for further clinical development. A more rational approach involves the defining of new targets, such as genes or enzymatic functions, responsible for a crucial cellular essential activity. Once this has been done, inhibitors or blockers of the function or gene product can be developed.

[0007] In order to identify potential targets for novel gram-negative antibacterial agents, studies aimed at identifying all essential and important genes in Pseudomonas aeruginosa have been performed. Among the essential genes identified was lpxC, that encodes the enzyme uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC). This enzyme is the first committed step in the synthesis of lipid A, the lipid moiety of lipopolysaccharide, that is an essential component of all gram-negative bacteria. It therefore is an attractive target for novel antibacterials. In order to be useful as antibacterial agents, LpxC inhibitors would not only have to inhibit the enzymatic activity of LpxC from a variety of bacteria, but would have to defeat the intrinsic resistance mechanisms of gram- negative bacteria, as described above: they would have to penetrate the outer membrane and be relatively unsusceptible to multidrug efflux pumps.

[0008] Researchers have identified a few compounds with antibacterial activity that target lipid A biosynthesis. WO 97/42179 to Patchett et al. discloses compounds of the formula: 2

[0009] The compounds possess activity against certain gram-negative organisms, for example Escherichia coli, but are not active against other medically important gram-negative bacteria, for example Pseudomonas aeruginosa. Subsequent studies have found that the primary reason for their inactivity against particular, medically important gram-negative bacteria is their poor ability to inhibit P. aeruginosa LpxC; efflux by the major multidrug efflux pump or inability to penetrate the outer membrane were not the critical factors.

[0010] Jackrnan et al., in J.Biol.Chem. (vol. 275, no. 15, Apr. 14, 2000, pps. 11002-11009), discuss the mechanism of lipid A biosynthesis in the context of gram-negative bacteria and discloses a new class of hydroxamate-containing inhibitors of LpxC. Wyckoffet al., in Trends in Microbiology (vol. 6, no. 4, April 1998, pps. 154-159), discuss the role of LpxC in lipid A biosynthesis and its role in regulation. Wyckoff et al. disclose a few oxazoline hydroxamic acids that inhibit bacterial growth. However, Wyckoff et al. also discuss the shortcomings of the available deacetylase inhibitors as bactericidal agents against Pseudomonas and that more work is needed to be done in the area.

[0011] Thus, an increasing need exists for LpxC inhibitors that have activity as bactericidal agents against gram-negative bacteria. It is, accordingly, an object. of this invention to provide compounds and combinations of such compounds for use in the preparation of antibacterials and other pharmaceuticals capable of inhibiting Gram-negative bacterial infections.

[0012] U.S. Patent Publication No. 2001/0053555 (U.S. patent application Ser. No. 08/958,638) published Dec. 20, 2001, corresponding to WO 98/18754 published May 7, 1998 discloses a combinatorial library of hydroxylamine, hydroxamic acid, hydroxyurea and hydroxylsulfonamide compounds purported to be potentially useful as inhibitors of metalloproteases. U.S. Pat. No. 6,281,245, a continuation in part of U.S. Ser. No. 08/958,638 claims a method of inhibiting a deformylase enzyme by administering one of the hydroxylamine compounds from the combinatorial library as disclosed in U.S. Patent Publication No. 2001/0053555 and the corresponding WO 98/18754. Related to the above disclosed patent publications is WO 99/57097, published Nov. 11, 1999, that discloses a method of solid phase synthesis of the hydroxylamine library of compounds. WO 00/61134 (to British Biotech Pharmaceuticals Limited), published Oct. 19, 2000, discloses compounds of the formula below: 3

[0013] The compounds are useful as antimicrobial agents that are believed to have bactericidal activity at least in part to intracellular inhibition of bacterial polypeptide deformylase.

[0014] In an earlier to British Biotech Pharmaceuticals Limited, WO 99/39704, published Aug. 12, 1999, compounds of the formula below are disclosed: 4

[0015] The compounds are useful as antimicrobial agents useful against gram-negative and gram positive bacteria.

[0016] Recently, De Novo Pharmaceuticals LTD disclosed in WO 02/50081, published Jun. 27, 2002, antibacterial and antiprotozoal agents having the formulae shown below: 5

[0017] The patent publication discusses that the antibacterial activity is due, at least in part, to intracellular inhibition of bacterial polypeptide deformylase.

SUMMARY OF THE INVENTION

[0018] The present invention provides novel compounds, pharmaceutical formulations including the compounds, methods of inhibiting UDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC), and methods of treating gram-negative bacterial infections.

[0019] In one embodiment, the present invention provides compounds of formula I: 6

[0020] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of

[0021] (1) H,

[0022] (2) substituted or unsubstituted C1-C6-alkyl,

[0023] (3) substituted or unsubstituted C2-C6-alkenyl,

[0024] (4) substituted or unsubstituted C2-C6-alkynyl,

[0025] (5) substituted-or unsubstituted aryl,

[0026] (6) substituted or unsubstituted heterocyclyl, and

[0027] (7) substituted or unsubstituted heteroaryl;

[0028] L is absent or selected from the group consisting of

[0029] (1) substituted or unsubstituted C1-C6-alkyl,

[0030] (2) —(NH)0-1—(CH2)j—NR3L—(CH2)k—,

[0031] (3) —(NH)0-1—C(R1L, R2)—NR3L—C(R1L, R2L)—,

[0032] (4) —C(R1L, R2L)—O—C(R1L, R2L)—,

[0033] (5) —(CH2)j—NR3L—C(R1L, R2L)—CONH—(CH2)k—,

[0034] (6) —CO—C(R1L, R2L)—NHCO—,

[0035] (7) —CONH—,

[0036] (8) —NHCO—,

[0037] wherein

[0038] R1L, R2L, and R3L are independently selected from the group consisting of

[0039] (a) H,

[0040] (b) substituted or unsubstituted C1-C6-alkyl,

[0041] (c) C1-C6-alkyl substituted with aryl,

[0042] (d) C1-C6-alkyl substituted with heterocyclyl, and

[0043] (e) C1-C6-alkyl substituted with heteroaryl,

[0044] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0045] j is an integer of 0-4;

[0046] k is an integer of 0-4;

[0047] D is absent or selected from the group consisting of

[0048] (1) substituted or unsubstituted C3-C8-cycloalkyl,

[0049] (2) substituted or unsubstituted aryl,

[0050] (3) substituted or unsubstituted heterocyclyl, and

[0051] (4) substituted or unsubstituted heteroaryl;

[0052] G is absent or selected from the group consisting of

[0053] (1) —(CH2)i—O—(CH2)i—,

[0054] (2) —(CH2)i—S—(CH2)i—,

[0055] (3) —(CH2)i—NRg—(CH2)i—,

[0056] (4) —C(═O)—,

[0057] (5) —NHC(═O)—,

[0058] (6) —(═O)NH—,

[0059] (7) —(CH2)iNHCH2C(═O)NH—,

[0060] (8) —C≡C—,

[0061] (9) —C≡C—C═C—, and

[0062] (10) —C═C—;

[0063] wherein

[0064] Rg is H or substituted or unsubstituted C1-C6-alkyl;

[0065] i is an interger of 0-4;

[0066] Y is selected from the group consisting of

[0067] (1) substituted or unsubstituted C3-C8-cycloalkyl,

[0068] (2) substituted or unsubstituted aryl,

[0069] (3) substituted or unsubstituted heterocyclyl, and

[0070] (4) substituted or unsubstituted heteroaryl;

[0071] X is selected from the group consisting of

[0072] (1) —(C═O)—,

[0073] (2) —C1-C6-alkyl—(C═O)—,

[0074] (3) —C2-C6-alkenyl—(C═O)—,

[0075] (4) —C2-C6-alkyyl-(C═O)—, and

[0076] (5) —CH2—;

[0077] or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0078] B is a absent or 7

[0079] wherein R1b and R2b, are independently selected fromr the group consisting of

[0080] (a) H,

[0081] (b) substituted or unsubstituted C1-C6-alkyl,

[0082] (c) substituted or unsubstituted C2-C6-alkenyl,

[0083] (d) substituted or unsubstituted C2-C6-alkynyl,

[0084] (e) substituted or unsubstituted aryl,

[0085] (f) substituted or unsubstituted heterocyclyl,

[0086] (g) substituted or unsubstituted heteroaryl,

[0087] (h) C1-C6-alkyl substituted with aryl,

[0088] (i) C1-C6-alkyl substituted with heterocyclyl, and

[0089] (j) C1-C6-alkyl substituted with heteroaryl,

[0090] or R1b and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, Q and S;

[0091] q is an integer of 0-4;

[0092] R3 is H or substituted or unsubstituted C1-C6-alkyl,

[0093] or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S;

[0094] R4 is H or substituted or unsubstituted C1-C6-alkyl,

[0095] or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0096] n is an integer of 0-6;

[0097] A is selected from the group consisting of

[0098] (1) H,

[0099] (2) —(CH2)rC(R1a, R1a)(CH2)(CH2)sOR3a,

[0100] (3) —(CH2)rC(R1a, R2a)N(R4a, R5a),

[0101] (4) —(CH2)rC(R1a, R2a)N(R4a)COR3a,

[0102] (5) —(CH2)rC(R1a, R2a)NHCON(R4a, R5a),

[0103] (6) —(CH2)rC(R1a, R2a)NHC(═NH)N(R4a, R5a),

[0104] (7) —CH(R1a, R2a),

[0105] (8) —C≡CH,

[0106] (9) —(CH2)rC(R1a, R2a)CN,

[0107] (10) —(CH2)rC(R1a, R2a)CO2R3a, and

[0108] (11) —(CH2)rC(R1a, R2a)CON(R4a, R5a),

[0109] wherein R1a, R2a, R3a, R4a, and R5a are independently selected from the group consisting of

[0110] (a) H,

[0111] (b) substituted or unsubstituted C1-C6-alkyl,

[0112] (c) substituted or unsubstituted aryl,

[0113] (d) substituted or unsubstituted heterocyclyl,

[0114] (e) substituted or unsubstituted heteroaryl,

[0115] (f) C1-C6-alkyl substituted with aryl,

[0116] (g) C1-C6-alkyl substituted with, heterocyclyl, and

[0117] (h) C1-C6-alkyl substituted.with heteroaryl,

[0118] or R4a and R5a together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0119] r is an integer of 0-4;

[0120] s is an integer of 0-4;

[0121] Q is absent or selected from the group consisting of

[0122] (1) —C(═O)N(R1, R2),

[0123] (2) —NHC(═O)N(R1, R2),

[0124] (3) 13 N(OH)C(═O)N(R1, R2),

[0125] (4) —CH(OH)C(═O)N(R1, R2),

[0126] (5) —CH[N(R2q, R3q)]C(═O)N(R1, R2),

[0127] (6) —CHR1qC(═O)N(R1, R2),

[0128] (7) —CO2H,

[0129] (8) —C(═O)NHSO2R4q,

[0130] (9) —SO2NH2,

[0131] (10) —N(OH)C(═O)R1q,

[0132] (11) —N(OH)SO2R4q,

[0133] (12) —NHSO2R4q,

[0134] (13) —SH,

[0135] (14) —CH(SH)(CH2)0-1C(═O)N(R1, R2),

[0136] (15) —CH(SH)(CH2)0-1CO2H,

[0137] (16) —CH(OH)(CH2)0-1CO2H,

[0138] (17) —CH(SH)CH2CO2R1q,

[0139] (18) —CH(OH)(CH2)SO2NH2,

[0140] (19) —CH(CH2SH)NHCOR1q,

[0141] (20) —CH(CH2SH)NHSO2R4q,

[0142] (21) —H(CH2SR5q)CO2H,

[0143] (22) —CH(CH2SH)NHSO2NH2,

[0144] (23) —H(CH2OH)CO2H,

[0145] (24) —CH(CH2OH)NHSO2NH2,

[0146] (25) —(═O)CH2CO2H,

[0147] (26) —C(═O)(CH2)0-1CONH2,

[0148] (27) —OSO2NHR5q,

[0149] (28) —SO2NHNH2,

[0150] (29) —P(═O)(OH)2, 8

[0151] (30)

[0152] (31)

[0153] (32)

[0154] wherein

[0155] R1 is selected from the group consisting of

[0156] (1) H,

[0157] (2) —OH,

[0158] (3) —OC1-6-alkyl,

[0159] (4) —N(R2q, R3q), and

[0160] (5) substituted or unsubstituted C1-6-alkyl;

[0161] R2 is selected from the group consisting of

[0162] (1) H,

[0163] (2) substituted or unsubstituted C1-C6-alkyl,

[0164] (3) substituted or unsubstituted C2-C6-alkenyl,

[0165] (4) substituted or unsubstituted C2-C6-alkenyl, (5) substituted or unsubstituted aryl,

[0166] (6) substituted or unsubstituted heterocyclyl,

[0167] (7) substituted or unsubstituted heteroaryl,

[0168] (8) C1-C6-alkyl substituted with aryl,

[0169] (9) C1-C6-alkyl substituted with heterocyclyl, and

[0170] (10) C1-C6-alkyl substituted with heteroaryl,

[0171] or R1 and R2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,

[0172] or R2 and R4, together with the N atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0173] R1q, R2q, R3q, R4q, and R5q are selected from H or C1-C6 alkyl,

[0174] wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

[0175] In one aspect, the invention provides a method of inhibiting a deacetylase enzyme in a gram-negative bacteria, thereby affecting bacterial growth, comprising administering to a patient in need of such inhibition a compound of formula I.

[0176] In another aspect, the invention provides a method of inhibiting LpxC, thereby modulating the virulence of a bacterial infection, comprising administering to a patient in need of such inhibition a compound of formula I.

[0177] In another aspect, the invention provides a method for treating a subject with a gram-negative bacterial infection comprising administering to the subject in need thereof an antibacterially effective amount of a compound of formula I with a pharmaceutically acceptable carrier. In a preferred embodiment of the method of treatment, the subject is a mammal and in some embodiments, a human.

[0178] In another aspect, the invention provides a method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermentative gram-negative bacteria. In a preferred embodiment of the method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermentative gram-negative bacteria, the gram-negative bacteria are selected from the group consisting of Pseudomonas aeruginosa, Stenotrophomonas maltophila, Burkholderia cepacia, Alcaligenes xylosoxidans, Acinetobacter, Enterobacteriaceae, Haemophilus, and Neisseria species.

[0179] In another embodiment, the invention provides a method of administering an inhibitory amount of a compound of formula I to gram-negative bacteria, such as Enterobacteriaceae which is selected from the group consisting of organisms such as Serratia, Proteus, Klebsiella, Enterobacter, Citrobacter, Salmonella, Providencia, Morganella, Cedecea, and Edwardsiella species and Escherichia coli.

[0180] Another embodiment of the invention provides a pharmaceutical composition comprising an effective amount of a compound of Formula I with a pharmaceutically acceptable carrier thereof.

[0181] Pharmaceutical formulations according to the present invention are provided which include any of the compounds described above in combination with a pharmaceutically acceptable carrier.

[0182] Another embodiment of the invention provides a method of co-administering the compound of formula I with other therapeutic agents that are selected for their particular usefulness against the condition that is being treated.

[0183] For example, the compound of formula I is useful in combination with other anti-bacterial agents. The compound of formula I augments the sensitivity of gram-negative bacteria to existing classes of antibacterials. Combinations of the presently disclosed compounds with other anti-bacterial. agents are within the scope of the invention. Such anti-bacterial agents include, but are not limited to, erythromycin, rifampicin, Nalidixic acid, carbenicillin, bacitracin, cycloserine, fosfomycin, and vancomycin.

DETAILED DESCRIPTION

[0184] The present invention provides novel compounds, methods for inhibiting LpxC in gram-negative bacteria, and novel methods for treating bacterial infections. The compounds provided herein can be formulated into pharmaceutical formulations and medicaments that are useful in the methods of the invention. The invention also provides for the use of the compounds in preparing medicaments and pharmaceutical formulations, for use of the compounds in inhibiting LpxC, and for use of the compounds in treating bacterial infections in a subject.

[0185] The following abbreviations and definitions are used throughout this application:

[0186] “LpxC” is an abbreviation that stands for UDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase.

[0187] Generally, reference to a certain element such as hydrogen or H is meant to include all isotopes of that element. For example, if an R group is defined to include hydrogen or H, it also includes deuterium and tritium.

[0188] The phrase “alkyl” refers to alkyl groups that-do not contain heteroatoms. Thus the phrase includes straight chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the like. The phrase also includes branched chain isomers of straight chain alkyl groups, including but not limited to, the following that are provided by way of example: —CH(CH3)2, —CH(CH3)(CH2CH3), —CH(CH2CH3)2, —C(CH3)3, —C(CH2CH3)3, —CH2CH(CH3)2, —CH2CH(CH3)(CH2CH3), —CH2CH(CH2CH3)2, —CH2C(CH3)3, —CH2C(CH2CH3)3, —CH(CH3)CH(CH3)(CH2CH3), —CH2CH2CH(CH3)2, —CH2CH2CH(CH3)(CH2CH3), —CH2CH2CH(CH2CH3)2, —CH2CH2C(CH3)3, —CH2CH2C(CH2CH3)3, —CH(CH3)CH2CH(CH3)2, —CH(CH3)CH(CH3)CH(CH3)2, —CH(CH2CH3)CH(CH3)CH(CH3)(CH2CH3), and others. The phrase also includes cyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl and such rings substituted with straight and branched chain alkyl groups as defined above. Thus the phrase alkyl groups includes primary alkyl groups, secondary alkyl groups, and tertiary alkyl groups. Preferred alkyl groups include straight and branched chain alkyl groups and cyclic alkyl groups having 1 to 12 carbon atoms.

[0189] The phrase “substituted alkyl” refers to an alkyl group as defined above in which one or more bonds to a carbon(s) or hydrogen(s) are replaced by a bond to non-hydrogen and non-carbon atoms such as, but not limited to, a halogen atom such as F, Cl, Br, and I; an oxygen atom in groups such as hydroxyl groups, alkoxy groups, aryloxy groups, and ester groups; a sulfur atom in groups such as thiol groups, alkyl and aryl sulfide groups, sulfone groups, sulfonyl groups, and sulfoxide groups; a nitrogen atom in groups such as amines, amides, alkylamines, dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides, imides, and enamines; a silicon atom in groups such as in trialkylsilyl groups, dialkylarylsilyl groups, alkyldiarylsilyl groups, and triarylsilyl groups; and other heteroatoms in various other groups. Substituted alkyl groups also include groups in which one or more bonds to a carbon(s) or hydrogen(s) atom is replaced by a higher-order bond (e.g., a double- or triple-bond) to a heteroatom such as oxygen in oxo, carbonyl, carboxyl, and ester groups; nitrogen in groups such as imines, oximes, hydrazones, and nitriles. Substituted alkyl groups further include alkyl groups in which one or more bonds to a carbon(s) or hydrogen(s) atoms is replaced by a bond to an aryl, heterocyclyl group, or cycloalkyl group. Preferred substituted alkyl groups include, among others, alkyl groups in which one or more bonds to a carbon or hydrogen atom is/are replaced by one or more bonds to fluorine atoms. Another preferred substituted alkyl group is the trifluoromethyl group and other alkyl groups that contain the trifluoromethyl group. Other preferred substituted alkyl groups include those in which one or more bonds to a carbon or hydrogen atom is replaced by a bond to an oxygen atom such that the substituted alkyl group contains a hydroxyl, alkoxy, or aryloxy group. Still other preferred substituted alkyl groups include alkyl groups that have an amine, or a substituted or unsubstituted alkylamine, dialkylamine, arylamine, (alkyl)(aryl)amine, diarylamine, heterocyclylamine, diheterocyclylamine, (alkyl)(heterocyclyl)amine, or (aryl)(heterocyclyl)amine group.

[0190] The phrase “alkenyl” refers to straight and branched chain and cyclic groups such as those described with respect to alkyl groups as defined above, except that at least one double bond exists between two carbon atoms. Examples include, but are not limited to vinyl, —CH═C(H)(CH3), —CH═C(CH3)2, —C(CH3)═C(H)2, —C(CH3)═C(H)(CH3), —C(CH2CH3)═CH2, cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl, and hexadienyl among others. The phrase “substituted alkenyl” has the same meaning with respect to alkenyl groups that substituted alkyl groups had with respect to unsubstituted alkyl groups. A substituted alkenyl group includes alkenyl groups in which a non-carbon or non-hydrogen atom is bonded to a carbon double bonded to another carbon and those in which one of the non-carbon or non-hydrogen atoms is bonded to a carbon not involved in a double bond to another carbon.

[0191] The phrase “alkynyl” refers to straight and branched chain groups such as those described with respect to alkyl groups as defined above, except that at least one triple bond exists between two carbon atoms. Examples include, but are not limited to —C≡C(H), —C≡C(CH3), —C≡C(CH2CH3), —C(H2)C≡C(H), —C(H)2C≡C(CH3), and —C(H)2C≡C(CH2CH3) among others. The phrase “substituted alkynyl” has the same meaning with respect to alkynyl groups that substituted alkyl groups had with respect to unsubstituted alkyl groups. A substituted alkynyl group includes alkynyl groups in which a non-carbon or non-hydrogen atom is bonded to a carbon triple bonded to another carbon and those in which a non-carbon or non-hydrogen atom is bonded to a carbon not involved in a triple bond to another carbon.

[0192] The phrase “heterocyclyl” refers to both aromatic and nonaromatic ring compounds including monocyclic, bicyclic, and polycyclic ring compounds such as, but not limited to, quinuclidinyl, containing 3 or more ring members of which one or more is a heteroatom such as, but not limited to, N, O, and S. Although the phrase “unsubstituted heterocyclyl” includes condensed heterocyclic rings such as benzimidazolyl, it does not include heterocyclyl groups that have other groups such as alkyl or halo groups bonded to one of the ring members as compounds such as 2-methylbenzimidazolyl are substituted heterocyclyl groups. Examples of heterocyclyl groups include, but are not limited to: unsaturated 3 to 8 membered rings containing 1 to 4 nitrogen atoms such as, but not limited to pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g. 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl etc.), tetrazolyl, (e.g. 1H-tetrazolyl, 2H tetrazolyl, etc.); saturated 3 to 8 membered rings containing 1 to 4 nitrogen atoms such as, but not limited to, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl; condensed unsaturated heterocyclic groups containing 1 to 4 nitrogen atoms such as, but not limited to, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl; unsaturated 3 to 8 membered rings containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms such as, but not limited to, oxazolyl, isoxazolyl, oxadiazolyl (e.g. 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.); saturated 3 to 8 membered rings containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms such as, but not limited to, morpholinyl; unsaturated condensed heterocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, benzoxazolyl, benzoxadiazolyl, benzoxazinyl (e.g. 2H-1,4-benzoxazinyl etc.); unsaturated 3 to 8 membered rings containing 1 to 3 sulfur atoms and 1 to 3 nitrogen atoms such as, but not limited to, thiazolyl, isothiazolyl, thiadiazolyl (e.g. 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.); saturated 3 to 8 membered rings containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms such as, but not limited to, thiazolodinyl; saturated and unsaturated 3 to 8 membered rings containing 1 to 2 sulfur atoms such as, but not limited to, thienyl, dihydrodithiinyl, dihydrodithionyl, tetrahydrothiophene, tetrahydrothiopyran; unsaturated condensed heterocyclic rings containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms such as, but not limited to, benzothiazolyl, benzothiadiazolyl, benzothiazinyl (e.g. 2H-1,4-benzothiazinyl, etc.), dihydrobenzothiazinyl (e.g. 2H-3,4-dihydrobenzothiazinyl, etc.), unsaturated 3 to 8 membered rings containing oxygen atoms such as, but not limited to furyl; unsaturated condensed heterocyclic rings containing 1 to 2 oxygen atoms such as benzodioxolyl (e.g. 1,3-benzodioxoyl, etc.); unsaturated 3 to 8 membered rings containing an oxygen atom and 1 to 2 sulfur atoms such as, but not limited to, dihydrooxathiinyl; saturated 3 to 8 membered rings containing 1 to 2 oxygen atoms and 1 to 2 sulfur atoms such as 1,4-oxathiane; unsaturated condensed rings containing 1 to 2 sulfur atoms such as benzothienyl, benzodithiinyl; and unsaturated condensed heterocyclic rings containing an oxygen atom and 1 to 2 oxygen atoms such as benzoxathiinyl. Heterocyclyl group also include those described above in which one or more S atoms in the ring is double-bonded to one or two oxygen atoms (sulfoxides and sulfones). For example, heterocyclyl groups include tetrahydrothiophene, tetrahydrothiophene oxide, and tetrahydrothiophene 1,1-dioxide. Preferred heterocyclyl groups contain 5 or 6 ring members. More preferred heterocyclyl groups include morpholine, piperazine, piperidine, pyrrolidine, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, thiomorpholine, thiomorpholine in which the S atom of the thiomorpholine is bonded to one or more 0 atoms, pyrrole, homopiperazine, oxazolidin-2-one, pyrrolidin-2-one, oxazole, quinuclidine, thiazole, isoxazole, furan, and tetrahydrofuran.

[0193] The phrase “substituted heterocyclyl” refers to a heterocyclyl group as defined above in which one of the ring members is bonded to a non-hydrogen atom such as described above with respect to substituted alkyl groups and substituted aryl groups. Examples, include, but are not limited to, 2-methylbenzimidazolyl, 5-methylbenzimidazolyl, 5-chlorobenzthiazolyl, 1-methyl piperazinyl, and 2-chloropyridyl among others.

[0194] The phrase “aryl” refers to aryl groups that do not contain heteroatoms. Thus the phrase includes, but is not limited to, groups such as phenyl, biphenyl, anthracenyl, naphthenyl by way of example. Although the phrase “unsubstituted aryl” includes groups containing condensed rings such as naphthalene, it does not include aryl groups that have other groups such as alkyl or halo groups bonded to one of the ring members, as aryl groups such as tolyl are considered herein to be substituted aryl groups as described below. A preferred unsubstituted aryl group is phenyl. Unsubstituted aryl groups may be bonded to one or more carbon atom(s), oxygen atom(s), nitrogen atom(s), and/or sulfur atom(s) in the parent compound, however.

[0195] The phrase “substituted aryl group” has the same, meaning with respect to unsubstituted aryl groups that substituted alkyl groups had with respect to unsubstituted alkyl groups. However, a substituted aryl group also includes aryl groups in which one of the aromatic carbons is bonded to one of the non-carbon or non-hydrogen atoms described above and also includes aryl groups in which one or more aromatic carbons of the aryl group is bonded to a substituted and/or unsubstituted alkyl, alkenyl, or alkynyl group as defined herein. This includes bonding arrangements in which two carbon atoms of an aryl group are bonded to two atorns of an alkyl, alkenyl, or alkynyl group to define a fused ring system (e.g. dihydronaphthyl or tetrahydronaphthyl). Thus, the phrase “substituted aryl” includes, but is not limited to tolyl, and hydroxyphenyl among others. Preferred substituents include straight and branched chain alkyl groups, —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, Br, —CF3, —N(CH3)2, —NHSO2CH3, —NHCOCH3.

[0196] The term “heteroaryl”, as used herein, refers to a cyclic or bicyclic aromatic radical having from five to ten ring atoms in each ring of which one atom of the cyclic or bicyclic ring is selected from S, O and N; zero, one or two ring atoms are additional heteroatoms independently selected from S, O and N; and the remaining ring atoms are carbon, the radical being joined to the rest of the molecule via any of the ring atoms, such as, for example, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isooxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, and naphthyridinyl, and the like.

[0197] The term “substituted heteroaryl” as used herein refers to a heteroaryl group as defined herein substituted by independent replacement of one, two or three of the hydrogen atoms thereon with Cl, Br, F, I, OH, CN, C1-C3-alkyl, C1-C6-alkoxy, C1-C6-alkoxy substituted with aryl, haloalkyl, thioalkoxy, amino, alkylamino, dialkylamino, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. In addition, any one substituent may be an aryl, heteroaryl, or heterocycloalkyl group. Preferred substituents include straight and branched chain alkyl groups, —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, Br, —CF3, —N(CH3)2, —NHSO2CH3, —NHCOCH3.

[0198] The term “biaryl” refers to a group or substituent to which two aryl groups, which are not condensed to each other, are bound. Exemplary biaryl compounds include, for example, phenylbenzene, diphenyldiazene, 4-methylthio- 1 -phenylbenzene, phenoxybenzene, (2-phenylethynyl)benzene, diphenyl ketone, (4-phenylbuta-1,3-diynyl)benzene, phenylbenzylamine, (phenylmethoxy)benzene, and the like. Preferred optionally substituted biaryl groups include: 2-(phenylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide, 1,4-diphenylbenzene, N-[4-(2-phenylethynyl)phenyl]-2-[benzylamino]acetamide, 2-amino-N-[4-(2-phenylethynyl)phenyl]propanamide, 2-amino-N-[4-(2-phenylethynyl)phenyl]acetamide, 2-(cyclopropylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide, 2-(ethylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide, 2-[(2-methylpropyl)amino]-N-[4-(2-phenylethynyl)phenyl]acetamide, 5-phenyl-2H-benzo[d]1,3-dioxolene, 2-chloro-1-methoxy4-phenylbenzene, 2-[(imidazolyhnethyl)amino]-N-[4-(2-phenylethynyl)phenyl]acetamide, 4-phenyl-1-phenoxybenzene, N-(2-aminoethyl)[4-(2-phenylethynyl)phenyl]carboxamide, 2-{[(4-fluorophenyl)methyl]amino}-N-[4-(2-phenylethynyl)phenyl]acetamide, 2-{[(4-methylphenyl)methyl]amino}-N-[4-(2-phenylethynyl)phenyl]acetamide, 4-phenyl-1-(trifluoromethyl)benzene, 1-butyl-4-phenylbenzene, 2-(cyclohexylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide, 2-(ethylmethylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide, 2-(butylamino)-N-[4-(2-phenylethynyl)phenyl]acetamide, N-[4-(2-phenylethynyl)phenyl]-2-(4-pyridylamino)acetamide, N-[4-(2-phenylethynyl)phenyl]-2-(quinuclidin-3-ylamino)acetamide, N-[4-(2-phenylethynyl)phenyl]pyrrolidin-2-ylcarboxamide, 2-amino-3-methyl-N-[4-(2-phenylethynyl)phenyl]butanamide, 4-(4-phenylbuta-1,3-diynyl)phenylamine, 2-(dimethylamino)-N-[4-(4-phenylbuta-1,3-diynyl)phenyl]acetamide, 2-(ethylamino)-N-[4-(4-phenylbuta- 1,3-diynyl)phenyl]acetamide, 4-ethyl-1-phenylbenzene, 1-[4-(2-phenylethynyl)phenyl]ethan-1-one, N-(1-carbamoyl-2-hydroxypropyl)[4-(4-phenylbuta-1,3-diynyl)phenyl]carboxamide, N-[4-(2-phenylethynyl)phenyl]propanamide, 4-methoxyphenyl phenyl ketone, phenyl-N-benzamide, (tert-butoxy)-N-[(4-phenylphenyl)methyl]carboxamide, 2-(3-phenylphenoxy)ethanehydroxamic acid, 3-phenylphenyl propanoate, 1-(4-ethoxyphenyl)-4-methoxybenzene, and [4-(2-phenylethynyl)phenyl]pyrrole.

[0199] The term “heteroarylaryl” refers to a biaryl group where one of the aryl groups. is a heteroaryl group. Exemplary heteroarylaryl groups include, for example, 2-phenylpyridine, phenylpyrrole, 3-(2-phenylethynyl)pyridine, phenylpyrazole, 5-(2-phenylethynyl)-1,3-dihydropyrimidine-2,4-dione, 4-phenyl-1,2,3-thiadiazole, 2-(2-phenylethynyl)pyrazine, 2-phenylthiophene, phenylimidazole, 3-(2-piperazinylphenyl)furan, 3-(2,4-dichlorophenyl)-4-methylpyrrole, and the like. Preferred optionally substituted heteroarylaryl groups include: 5-(2-phenylethynyl)pyrimidine-2-ylamine, 1-methoxy-4-(2-thienyl)benzene, 1-methoxy-3-(2-thienyl)benzene, 5-methyl-2-phenylpyridine, 5-methyl-3-phenylisoxazole, 2-[3-(trifluoromethyl)phenyl]furan, 3-fluoro-5-(2-furyl)-2-methoxy-1-prop-2-enylbenzene, (hydroxyimino)(5-phenyl(2-thienyl))methane, 5-[(4-methylpiperazinyl)methyl]-2-phenylthiophene, 2-(4-ethylphenyl)thiophene, 4-methylthio-1-(2-thienyl)benzene, 2-(3-nitrophenyl)thiophene, (tert-butoxy)-N-[(5-phenyl(3-pyridyl))methyl]carboxamide, hydroxy-N-[(5-phenyl(3-pyridyl))methyl]amide, 2-(phenylmethylthio)pyridine, and benzylimidazole.

[0200] The term “heteroarylheteroaryl” refers to a biaryl group where both of the aryl groups is a heteroaryl group. Exemplary heteroarylheteroaryl groups include, for example, 3-pyridylimidazole, 2-imidazolylpyrazine, and the like. Preferred optionally substituted heteroarylheteroaryl groups include: 2-(4-piperazinyl-3-pyridyl)furan, diethyl(3-pyrazin-2-yl(4-pyridyl))amine, and dimethyl{2-[2-(5-methylpyrazin-2-yl)ethynyl](4-pyridyl)}amine.

[0201] “Optionally substituted” refers to the optional replacement of hydrogen with one or more monovalent or divalent radicals. Optionally substituted groups include those described herein, for each group in which a distinct definition for substitution is supplied. Additionally, suitable substitution groups include, for example, hydroxyl, nitro, amino, imino, cyano, halo, thio, thioamido, amidino, imidino, oxo, oxamidino, methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, alkyl, substituted alkyl, haloloweralkyl, loweralkoxy, haloloweralkoxy, loweralkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, alkylthio, aminoalkyl, cyanoalkyl, benzyl, pyridyl, pyrazolyl, pyrrole, thiophene, imidazolyl, and the like.

[0202] Representative substituted amidino and heterocycloamidino groups include, for example, those shown below. These amidino and heterocycloamidino groups can be further substituted as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein. 9

[0203] Representative substituted alkylcarbonylamino, alkyloxycarbonylamino, aminoalkyloxycarbonylamino, and arylcarbonylamino groups include, for example, those shown below. These groups can be further substituted as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein. 10

[0204] Representative substituted aminocarbonyl groups include, for example, those shown below. These can be further substituted by heterocyclo groups and heteroaryl groups as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein. Prefered aminocarbonyl groups include: N-(2-cyanoethyl)carboxamide, N-(3-methoxypropyl)carboxamide, N-cyclopropylcarboxamide, N-(2-hydroxy-isopropyl)carboxamide, methyl 2-carbonylamino-3-hydroxypropanoate, N-(2-hydroxypropyl)carboxamide, N-(2-hydroxy-isopropyl)carboxamide, N-[2-hydroxy-1-(hydroxymethyl)ethyl]carboxamide, N-(2-carbonylaminoethyl)acetamide, N-(2-(2-pyridyl)ethyl)carboxamide, N-(2-pyridylmethyl)carboxamide, N-(oxolan-2-ylmethyl)carboxamide, N-(4-hydroxypyrrolidin-2-yl)carboxamide, N-[2-(2-hydroxyethoxy)ethyl]carboxamide, N-(4-hydroxycyclohexyl)carboxamide, N-[2-(2-oxo4-imidazolinyl)ethyl]carboxamide, N-(carbonylaminomethyl)acetamide, N-(3-pyrrolidinylpropyl)carboxamide, N-[1-(carbonylaminomethyl)pyrrolidin-3-yl]acetamide, N-(2-morpholin4-ylethyl)carboxamide, N-[3-(2-oxopyrrolidinyl)propyl]carboxamide, 4-methyl-2-oxopiperazinecarbaldehyde, N-(2-hydroxy-3-pyrrolidinylpropyl)carboxamide, N-(2-hydroxy-3-morpholin-4-ylpropyl)carboxamide, N-{2-[(5-cyano-2-pyridyl)atnino]ethyl}carboxamide, 3-(dimethylamino)pyrrolidinecarbaldehyde, N-[(5-methylpyrazin-2-yl)methyl]carboxamide, 2,2,2-trifluoro-N-(1-formylpyrrolidin-3-yl)acetamide, 11

[0205] Representative substituted alkoxycarbonyl groups include, for example, those shown below. These alkoxycarbonyl groups can be further substituted as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein. 12

[0206] The term “protected” with respect to hydroxyl groups, amine groups, and sulfhydryl groups refers to forms of these functionalities that are protected from undesirable reaction with a protecting group known to those skilled in the art such as those set forth in Protective Groups in Organic Synthesis, Greene, T. W.; Wuts, P. G. M., John Wiley & Sons, New York, NY, (3rd Edition, 1999) that can be added or removed using the procedures set forth therein. Examples of protected hydroxyl groups include, but are not limited to, silyl ethers such as those obtained by reaction of a hydroxyl group with a reagent such as, but not limited to, t-butyldimethyl-chlorosilane, trimethylchlorosilane, triisopropylchlorosilane, triethylchlorosilane; substituted methyl and ethyl ethers such as, but not limited to methoxymethyl ether, methythiomethyl ether, benzyloxymethyl ether, t-butoxymethyl ether, 2-methoxyethoxymethyl ether, tetrahydropyranyl ethers, 1-ethoxyethyl ether, allyl ether, benzyl ether; esters such as, but not limited to, benzoylformate, formate, acetate, trichloroacetate, and trifluoracetate. Examples of protected amine groups include, but are not limited to, amides such as, formamide, acetamide, trifluoroacetamide, and benzamide; imides, such as phthalimide, and dithiosuccinimide; and others. Examples of protected sulfhydryl groups include, but are not limited to, thioethers such as S-benzyl thioether, and S-4-picolyl thioether; substituted S-methyl derivatives such as hemithio, dithio and aminothio acetals; and others.

[0207] A “pharmaceutically acceptable salt” includes a salt with an inorganic base, organic base, inorganic acid, organic acid, or basic or acidic amino acid. As salts of inorganic bases, the invention includes, for example, alkali metals such as sodium or potassium; alkaline earth metals such as calcium and magnesium or aluminum; and ammonia. As salts of organic bases, the invention includes, for example, trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, and triethanolamine. As salts of inorganic acids, the instant invention includes, for example, hydrochloric acid, hydroboric acid, nitric acid, sulfuric acid, and phosphoric acid. As salts of organic acids, the instant invention includes, for example, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. As salts of basic amino acids, the instant invention includes, for example, arginine, lysine and omithine. Acidic amino acids include, for example, aspartic acid and glutamic acid.

[0208] As used herein, the term “pharmaceutically acceptable ester” refers to esters that hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which each alkyl or alkenyl moiety advantageously has not more than 6 carbon atoms. Representative examples of particular esters include, but are not limited to, formates, acetates, propionates, butyrates, acrylates and ethylsuccinates.

[0209] The term “pharmaceutically acceptable prodrugs” as used herein refers to those prodrugs of the compounds of the present invention that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term “prodrug” refers to compounds that are rapidly transformed in vivo to yield the parent compound of the above formnula, for example by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference.

[0210] The term “antibacterial agent” refers to agents synthesized or modified in the laboratory that have either bactericidal or bacteriostatic activity. An “active” agent in this context will inhibit the growth of P. aeruginosa and other gram-negative bacteria. The term “inhibiting the growth” indicates that the rate of increase in the numbers of a population of a particular bacterium is reduced. Thus, the term includes situations in which the bacterial population increases but at a reduced rate, as well as situations where the growth of th& population is stopped, as well as situations where the numbers of the bacteria in the population are reduced or the population even eliminated. If an enzyme activity assay is used to screen for inhibitors, one can make modifications in uptake/efflux, solubility, half-life, etc. to compounds in order to correlate enzyme inhibition with growth inhibition. The activity of antibacterial agents is not necessarily limited to bacteria but may also encompass activity against parasites, virus, and fungi.

[0211] The subject invention also includes isotopically-labeled LpxC inhibitors, that are structurally identical to those disclosed above, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine and chlorine, such as 2H, 3H, 13C, 14C, 15N, 18O, 17O, 31P, 32P, 35S, 18F and 36Cl, respectively. Compounds of the present invention, prodrugs thereof, and pharmaceutically acceptable salts of said compounds and of said prodrugs that contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically labeled compounds of the present invention, for example those into which radioactive isotopes such as 3H and 14C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., 3H, and carbon-14, i.e., 14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., 2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labeled compounds of this invention and prodrugs thereof can generally be prepared by carrying out known or referenced procedures and by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

[0212] The present invention provides novel compounds, pharmaceutical formulations including the compounds, methods of inhibiting UDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC), and methods of treating gram-negative bacterial infections.

[0213] In one embodiment, the present invention provides compounds of formula I: 13

[0214] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of

[0215] (1) H,

[0216] (2) substituted or unsubstituted C1-C6-alkyl,

[0217] (3) substituted or unsubstituted C2-C6-alkenyl,

[0218] (4) substituted or unsubstituted C2-C6-alkynyl,

[0219] (5) substituted or unsubstituted aryl,

[0220] (6) substituted or unsubstituted heterocyclyl, and

[0221] (7) substituted or unsubstituted heteroaryl;

[0222] L is absent or selected from the group consisting of

[0223] (1) substituted or unsubstituted C1-C6-alkyl,

[0224] (2) —(NH)0-1—(CH2)j—NR3L—(CH2)k—,

[0225] (3) —(NH)0-1—C(R1L, R2L)—NR3L—C(R1L, R2L)—,

[0226] (4) —C(R1L, R2L)—O—C(R1L, R2L)—,

[0227] (5) —CH2)j—NR3L—C(R1L, R2L)—CONH—(CH2)k—,

[0228] (6) —CO—C(R1L, R2L)—NHCO—,

[0229] (7) —CONH—,

[0230] (8) —NHCO—,

[0231] wherein

[0232] R1L, R2L, and R3L are independently selected from the group consisting of

[0233] (a) H,

[0234] (b) substituted or unsubstituted C1-C6-alkyl,

[0235] (c) C1-C6-alkyl substituted with aryl,

[0236] (d) C1-C6-alkyl substituted with heterocyclyl, and

[0237] (e) C1-C6-alkyl substituted with heteroaryl,

[0238] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S,

[0239] j is an integer of 0-4;

[0240] k is an integer of 0-4;

[0241] D is absent or selected from the group consisting of

[0242] (1) substituted or unsubstituted C3-C8-cycloalkyl,

[0243] (2) substituted or unsubstituted aryl,

[0244] (3) substituted or unsubstituted heterocyclyl, and

[0245] (4) substituted or-unsubstituted heteroaryl;

[0246] G is absent or selected from the group consisting of

[0247] (1) —(CH2)i—O—(CH2)i—,

[0248] (2) —(CH2)i—S—(CH2)i—,

[0249] (3) —(CH2)i—NRg—(CH2)i—,

[0250] (4) —C(═O)—,

[0251] (5) —NHC(═O)—,

[0252] (6) —C(═O)NH—,

[0253] (7) —CH2)iNHCH2C(═O)NH—,

[0254] (8) —C≡C—,

[0255] (9) —C≡C—C≡C—, and

[0256] (10) —C═C—;

[0257] wherein

[0258] Rg is H or substituted or unsubstituted C1-C6-alkyl; i is an interger of 0-4;

[0259] Y is selected from the group consisting of

[0260] (1) substituted or unsubstituted C3-C8-cycloalkyl,

[0261] (2) substituted or unsubstituted aryl,

[0262] (3) substituted or unsubstituted heterocyclyl, and

[0263] (4) substituted or unsubstituted heteroaryl;

[0264] X is selected from the group consisting of

[0265] (1) —(C═O)—,

[0266] (2) —C1-C6-alkyl-(C═O)—,

[0267] (3) —C2-C6-alkenyl-(C═O)—,

[0268] (4) —C2-C6-alkynyl-(C═O)—, and

[0269] (5) —CH2—;

[0270] or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0271] B is a absent or 14

[0272] wherein R1b and R2b, are independently selected from the group consisting of

[0273] (a) H,

[0274] (b) substituted or unsubstituted C1-C6-alkyl,

[0275] (c) substituted or unsubstituted C2-C6-alkenyl,

[0276] (d) substituted or unsubstituted C2-C6-allynyl,

[0277] (e) substituted or unsubstituted aryl,

[0278] (f) substituted or unsubstituted heterocyclyl,

[0279] (g) substituted or unsubstituted heteroaryl,

[0280] (h) C1-C6-alkyl substituted with aryl,

[0281] (i) C1-C6-alkyl substituted with heterocyclyl, and

[0282] (j) C1-C6-alkyl substituted with heteroaryl,

[0283] or R1b and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic: ring system are selected from N, O and S;

[0284] q is an integer of 0-4;

[0285] R3 is H or substituted or unsubstituted C1-C6-alkyl, or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S;

[0286] R4 is H or substituted or unsubstituted C1-C6-alkyl, or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0287] n is an integer of 0-2;

[0288] A is selected from the group consisting of

[0289] (1) H,

[0290] (2) —(CH2)rC(R1a, R2a)(CH2)sOR3a,

[0291] (3) —(CH2)rC(R1a, R2a)N(R4a, R5a),

[0292] (4) —(CH2)rC(R1a, R2a)N(R4a)COR3a,

[0293] (5) —(CH2)rC(R1a, R2a)NHCON(R4a, R5a),

[0294] (6) —(CH2)rC(R1a, R2a)NHC(═NH)N(R4a, R5a),

[0295] (7) —CH(R1a, R2a),

[0296] (8) —C≡CH,

[0297] (9) —CH2)rC(R1a, R2a)CN,

[0298] (10) —CH2)rC(R1a, R2a)CO2R3a, and

[0299] (11) —CH2)rC(R1a, R2a)CN(R4a, R5a),

[0300] wherein R1a, R2a, R3a, R4a, and R5a are independently selected from the group consisting of

[0301] (a) H,

[0302] (b) substituted or unsubstituted C1-C6-alkyl,

[0303] (c) substituted or unsubstituted aryl,

[0304] (d) substituted or unsubstituted heterocyclyl,

[0305] (e) substituted or unsubstituted heteroaryl,

[0306] (f) C1-C6-alkyl substituted with aryl,

[0307] (g) C1-C6-alkyl substituted with heterocyclyl, and

[0308] (h) C1-C6-alkyl substituted with heteroaryl,

[0309] or R4a and R5a together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0310] r is an integer of 0-4;

[0311] s is an integer of 0-4;

[0312] Q is absent or selected from the group consisting of

[0313] (1) —C(═O)N(R1, R2),

[0314] (2) —NHC(═O)N(R1, R2),

[0315] (3) —N(OH)C(═O)N(R1, R2),

[0316] (4) —CH(OH)C(═O)N(R1, R2),

[0317] (5) —CH[NR2q, R3q)]C(═O)N(R1, R2),

[0318] (6) —CHR1qC(═O)N(R1, R2),

[0319] (7) —CO2H,

[0320] (8) —C(═O)NHSO2R4q,

[0321] (9) —SO2NH2,

[0322] (10) —N(OH)C(═O)R1q,

[0323] (11) —N(OH)SO2R4q,

[0324] (12) —NHSO2R4q,

[0325] (13) —SH,

[0326] (14) —CH(SH)(CH2)0-1C(═O)N(R1, R2),

[0327] (15) —CH(SH)(CH2)0-1CO2H,

[0328] (16) —CH(OH)(CH2)0-1CO2H,

[0329] (17) —CH(SH)CH2CO2R1q,

[0330] (18) —CH(OH)(CH2)SO2NH2,

[0331] (19) —CH(CH2SH)NHCOR1q,

[0332] (20) —CH(CH2SH)NHSO2R4q,

[0333] (21) —CH(CH2SR5q)CO2H,

[0334] (22) —CH(CH2SH)NHSO2NH2,

[0335] (23) —CH(CH2OH)CO2H,

[0336] (24) —CH(CH2OH)NHSO2NH2,

[0337] (25) —C(═O)CH2CO2H,

[0338] (26) —C(═O)(CH2)0-1CONH2,

[0339] (27) —OSO2NHR5q,

[0340] (28) —SO2NHNH2,

[0341] (29) —P(═O)(OH)2, 15

[0342] (30)

[0343] (31)

[0344] (32)

[0345] R1 is selected from the group consisting of

[0346] (1) —H,

[0347] (2) —OH,

[0348] (3) —OC1-6-alkyl,

[0349] (4) —N(R2q, R3q), and

[0350] (5) substituted or unsubstituted C1-6-alkyl;

[0351] R2 is selected from the group consisting of

[0352] (1) H,

[0353] (2) substituted or unsubstituted C1-C6-alkyl,

[0354] (3) substituted or unsubstituted C2-C6-alkenyl,

[0355] (4) substituted or unsubstituted C2-C6-alkenyl,

[0356] (5) substituted or unsubstituted aryl,

[0357] (6) substituted or unsubstituted heterocyclyl,

[0358] (7) substituted or unsubstituted heteroaryl,

[0359] (8) C1-C6-alkyl substituted with aryl,

[0360] (9) C1-C6-alkyl substituted with heterocyclyl, and

[0361] (10) C1-C6-alkyl substituted with heteroaryl,

[0362] or R1 and R2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,

[0363] R1q, R2q, R3q, R4q, and R5q are selected from H or C1-C6 alkyl,

[0364] wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

[0365] In another embodiment, the present invention provides compounds of formula I: 16

[0366] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein

[0367] E is absent or selected from the group consisting of

[0368] (1) H,

[0369] (2) substituted or unsubstituted C1-C6-alkyl,

[0370] (3) substituted or unsubstituted aryl,

[0371] (4) substituted or unsubstituted heterocyclyl, and

[0372] (5) substituted or unsubstituted heteroaryl;

[0373] L is absent or selected from the group consisting of

[0374] (1) —(CH2)j—NR3L—(CH2)k—,

[0375] (2) —C(R1L, R2L)j—NR3L—C(R1L, R2L)k—,

[0376] (3) —C(R1L, R2L)j—O—C(R1L, R2L)k—,

[0377] (4) —(CH2)j—NR3L—C(R1L, R2L)k—CONH—(CH2)k—,

[0378] (5) —CO—C(R1L, R2L)—NHCO—,

[0379] (6) —CONH—, and

[0380] (7) —NHCO—,

[0381] wherein

[0382] R1L, R2L, R3L are independently selected from the group consisting of

[0383] (a) H,

[0384] (b) substituted or unsubstituted C1-C6-alkyl,

[0385] (c) C1-C6-alkyl substituted with aryl,

[0386] (d) C1-C6-alkyl substituted with heterocyclyl,

[0387] (e) C1-C6-alkyl substituted with heteroaryl,

[0388] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0389] j is an integer of 0-4;

[0390] k is an integer of 0-4;

[0391] D is absent or selected from the group consisting of

[0392] (1) substituted or unsubstituted C3-C8-cycloalkyl,

[0393] (2) substituted or unsubstituted aryl,

[0394] (3) substituted or unsubstituted heterocyclyl,

[0395] (4) substituted or unsubstituted heteroaryl, and

[0396] G is absent or selected from the group consisting of

[0397] (1) —C(═O)—,

[0398] (2) —NHC(═O)—,

[0399] (3) —C(═O)NH—,

[0400] (4) —(CH2)iNHCH2C(═O)NH—,

[0401] (5) —C≡C—, and

[0402] (6) —C≡C—C≡C—,

[0403] wherein i is an interger of 0-4;

[0404] Y is selected from the group consisting of

[0405] (1) substituted or unsubstituted C3-C8-cycloalkyl,

[0406] (2) substituted or unsubstituted aryl,

[0407] (3) substituted or unsubstituted heterocyclyl, and

[0408] (4) substituted or unsubstituted heteroaryl;

[0409] X is selected from the group consisting of

[0410] (1) —(C═O)—,

[0411] (2) —C1-C6-alkyl-(C═O)—,

[0412] (3) —C2-C26-alkenyl-(C═O)—,

[0413] (4) —C2-C6-alkynyl-(C═O), and

[0414] (5) —CH2—;

[0415] or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0416] B is absent or 17

[0417] wherein R1b and R2b are independently selected from the group consisting of

[0418] (a) H

[0419] (b) substituted or unsubstituted C1-C6-alkyl,

[0420] (c) substituted or unsubstituted C2-C6-alkenyl,

[0421] (d) substituted or unsubstituted C2-C6-alkenyl,

[0422] (e) substituted or unsubstituted aryl,

[0423] (f) substituted or unsubstituted heterocyclyl,

[0424] (g) substituted or unsubstituted heteroaryl,

[0425] (h) C1-C6-alkyl substituted with aryl,

[0426] (i) C1-C6-alkyl substituted with heterocyclyl, and

[0427] (i) C1-C6-alkyl substituted with heteroaryl,

[0428] or R1b and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted.heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0429] q is an integer of 0-2;

[0430] R3 is H or substituted or unsubstituted C1-C6-alkyl,

[0431] or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S;

[0432] R4 is H or substituted or unsubstituted C1-C6-alkyl,

[0433] or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0434] A is selected from the group consisting of

[0435] (1) H,

[0436] (2) —(CH2)rC(R1a, R2a)(CH2)sOR3a,

[0437] (3) —(CH2)rC(R1a, R2a)N(R4a, R5a),

[0438] (4) —(CH2)rC(R1a, R2a)N(R4a)COR3a,

[0439] (5) —(CH2)rC(R1a, R2a)NHCON(R4a, R5a),

[0440] (6) —(CH2)rC(R1a, R2a)NHC(═NH)N(R4a, R5a),

[0441] (7) —(CH(R1a, R2a),

[0442] (8) —C≡CH,

[0443] (9) —(CH2)rC(R1a, R2a)CN, and

[0444] (10) —(CH2)rC(R1a, R2a)CO2R3a,

[0445] wherein R1a, R2a, R3a, R4a, and R5a, are independently selected from the group consisting of

[0446] (a) H,

[0447] (b) substituted or unsubstituted C1-C6-alkyl,

[0448] (c) C -C6-alkyl substituted with aryl,

[0449] (d) C1-C6-alkyl substituted with heterocyclyl, and

[0450] (e) C1-C6-alkyl substituted with heteroaryl,

[0451] or R4a and R5a, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0452] r is an integer of 0-4;

[0453] Q is absent or selected from the group consisting of

[0454] (1) —C(═O)N(R1, R2),

[0455] (2) —NHC(═O)N(R1, R2),

[0456] (3) —N(OH)C(═O)N(R1, R2),

[0457] (4) —CH(OH)C(═O)N(R1, R2),

[0458] (5) —CHR2q, R3q)]C(═O)N(R1, R2), and

[0459] (6) —CHR1qC(═O)N(R1, R2),

[0460] R1 is selected from the group consisting of

[0461] (1) H,

[0462] (2) OH,

[0463] (3) OC1-6-alkyl,

[0464] (4) N(R2q, R3q), and

[0465] (5) substituted or unsubstituted C1-6-alkyl;

[0466] R2 is selected from the group consisting of

[0467] (1) H,

[0468] (2) substituted or unsubstituted C1-C6-alkyl,

[0469] (3) substituted or unsubstituted aryl,

[0470] (4) substituted or unsubstituted heterocyclyl,

[0471] (5) substituted or unsubstituted heteroaryl,

[0472] (6) C1-C6-alkyl substituted with aryl,

[0473] (7) C1-C6-alkyl substituted with heterocyclyl, and

[0474] (8) C1-C6-alkyl substituted with heteroaryl,

[0475] or R1 and R2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,

[0476] R1q, R2q, and R3q are selected from H or C1-C6 alkyl,

[0477] wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

[0478] In another embodiment, the present invention provides compounds of formula II: 18

[0479] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of 19 20 21 22 23

[0480] Wherein

[0481] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0482] X is selected from the group consisting of

[0483] (1) —(C═O)—,

[0484] (2) —C1-C6-alkyl-(C═O)—, and

[0485] (3) —C2-C6-alkenyl-(C═O)—.

[0486] In another embodiment, the present invention provides compounds of formula III: 24

[0487] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of 25 26 27 28 29

[0488] Wherein

[0489] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0490] X is selected from the groups consisting of

[0491] (1) —(C═O)—,

[0492] (2) —C1-C6-alkyl-(C═O)—, and

[0493] (3) —C2-C6-alkenyl-(C═O)—.

[0494] In another embodiment, the present invention provides compounds of formula IV: 30

[0495] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of 31 32 33 34 35

[0496] Wherein

[0497] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0498] X is selected from the groups consisting of

[0499] (1) —(C═O)—,

[0500] (2) —C1-C6-alkyl-(C═O)—, and

[0501] (3) —C2-C6-alkenyl-(C═O)—.

[0502] In another embodiment, the present invention provides compounds of formula V: 36

[0503] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of 37 38 39 40 41

[0504] Wherein

[0505] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0506] X is selected from the groups consisting of

[0507] (1) —(C═O)—,

[0508] (2) —C1-C6-alkyl-(C═O)—, and

[0509] (3) —C2-C6-alkenyl-(C═O)—.

[0510] In another embodiment, the present invention provides compounds of formula VI: 42

[0511] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of

[0512] (1) H,

[0513] (2) substituted or unsubstituted C1-C6-alkyl,

[0514] (3) substituted or unsubstituted aryl,

[0515] (4) substituted or unsubstituted heterocyclyl, and

[0516] (5) substituted or unsubstituted heteroaryl,

[0517] or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,

[0518] R1L, R3L are independently selected from the group consisting of

[0519] (1) H,

[0520] (2) substituted or unsubstituted C1-C6-alkyl,

[0521] (3) C1-C6-alkyl substituted with aryl,

[0522] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0523] (5) C1-C6-alkyl substituted with heteroaryl,

[0524] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

[0525] In another embodiment, the present invention provides compounds of formula VII: 43

[0526] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of

[0527] (1) H,

[0528] (2) substituted or unsubstituted C1-C6-alkyl,

[0529] (3) substituted or unsubstituted aryl,

[0530] (4) substituted or unsubstituted heterocyclyl, and

[0531] (5) substituted or unsubstituted heteroaryl,

[0532] or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0533] R1L, R3L are independently selected from the group consisting of

[0534] (1) H,

[0535] (2) substituted or unsubstituted C1-C6-alkyl,

[0536] (3) C1-C6-alkyl substituted with aryl,

[0537] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0538] (5) C1-C6-alkyl substituted with heteroaryl,

[0539] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

[0540] In another embodiment, the present invention provides compounds of formula VIII: 44

[0541] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein

[0542] E is absent or selected from the group consisting of

[0543] (1) H,

[0544] (2) substituted or unsubstituted C1-C6-alkyl,

[0545] (3) substituted or unsubstituted aryl,

[0546] (4) substituted or unsubstituted heterocyclyl, and

[0547] (5) substituted or unsubstituted heteroaryl,

[0548] or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0549] R1L, R3L are independently selected from the group consisting of

[0550] (1) H,

[0551] (2) substituted or unsubstituted C1-C6-alkyl,

[0552] (3) C1-C6-alkyl substituted with aryl,

[0553] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0554] (5) C1-C6-alkyl substituted with heteroaryl,

[0555] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

[0556] In another embodiment, the present invention provides compounds of formula IX: 45

[0557] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of

[0558] (1) H,

[0559] (2) substituted or unsubstituted C1-C6-alkyl,

[0560] (3) substituted or unsubstituted aryl,

[0561] (4) substituted or unsubstituted heterocyclyl, and

[0562] (5) substituted or unsubstituted heteroaryl,

[0563] or E and R3L, together with the atoms to which, they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0564] R1L, R3L are independently selected from the group consisting of

[0565] (1) H,

[0566] (2) substituted or unsubstituted C1-C6-alkyl,

[0567] (3) C1-C6-alkyl substituted with aryl,

[0568] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0569] (5) C1-C6-alkyl substituted with heteroaryl,

[0570] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

[0571] In another embodiment, the present invention provides compounds of formula X: 46

[0572] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of

[0573] (1) H1,

[0574] (2) substituted or unsubstituted C1-C6-alkyl,

[0575] (3) substituted or unsubstituted aryl,

[0576] (4) substituted or unsubstituted heterocyclyl, and

[0577] (5) substituted or unsubstituted heteroaryl,

[0578] or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

[0579] R1L, R3L are independently selected from the group consisting of

[0580] (1) H,

[0581] (2) substituted or unsubstituted C1-C6-alkyl,

[0582] (3) C1-C6-alkyl substituted with aryl,

[0583] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0584] (5) C1-C6-alkyl substituted with heteroaryl,

[0585] or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted-heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

[0586] In another embodiment, the present invention provides compounds of formula XI: 47

[0587] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein Y—X taken together, is selected from the group consisting of 48 49

[0588] In another embodiment, the present invention provides compounds of formula XII: 50

[0589] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein R1b and R2b are independently selected from the group consisting of

[0590] (1) H,

[0591] (2) substituted or unsubstituted C1-C6-alkyl,

[0592] (3) substituted or unsubstituted C2-C6-alkenyl,

[0593] (4) substituted or unsubstituted C2-C6-alkenyl,

[0594] (5) substituted or unsubstituted aryl,

[0595] (6) substituted or unsubstituted heterocyclyl,

[0596] (7) substituted or unsubstituted heteroaryl,

[0597] (8) C1-C6-alkyl substituted with aryl,

[0598] (9) C1-C6-alkyl substituted with heterocyclyl, and

[0599] (10) C1-C6-alkyl substituted with heteroaryl;

[0600] q is an integer of 0-2;

[0601] In another embodiment, the present invention provides compounds of formula XIII: 51

[0602] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein

[0603] R4 is selected from the group consisting of

[0604] (1) H,

[0605] (2) substituted or unsubstituted C1-C6-alkyl,

[0606] (3) C1-C6-alkyl substituted with aryl,

[0607] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0608] (5) C1-C6-alkyl substituted with heteroaryl;

[0609] A is H or —CH(CH3)OH—;

[0610] R1 is H or substituted or unsubstituted C1-6-alkyl;

[0611] R2 is selected from the group consisting of

[0612] (1) H,

[0613] (2) substituted or unsubstituted C1-C6-alkyl,

[0614] (3) substituted or unsubstituted aryl,

[0615] (4) substituted or unsubstituted heterocyclyl,

[0616] (5) substituted or unsubstituted heteroaryl,

[0617] (6) C1-C6-alkyl substituted with aryl,

[0618] (7) C1-C6-alkyl substituted with heterocyclyl,

[0619] (8) C1-C6-alkyl substituted with heteroaryl,

[0620] or R1 and R2 together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

[0621] In another embodiment, the present invention provides compounds of formula XIV: 52

[0622] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together is selected from the group consisting of 53 54 55 56 57

[0623] Wherein

[0624] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0625] R4 is selected from the group consisting of

[0626] (1) H,

[0627] (2) substituted or unsubstituted C1-C6-alkyl,

[0628] (3) C1-C6-alkyl substituted with aryl,

[0629] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0630] (5) C1-C6-alkyl substituted with heteroaryl.

[0631] In another embodiment, the present invention provides compounds of formula XV: 58

[0632] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of 59 60 61 62 63

[0633] Wherein

[0634] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3,—OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0635] In another embodiment, the present invention provides compounds of formula XVI: 64

[0636] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of 65 66 67 68 69

[0637] Wherein

[0638] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0639] R4 is selected from the group consisting of

[0640] (1) H,

[0641] (2) substituted or unsubstituted C1-C6-alkyl,

[0642] (3) C1-C6-alkyl substituted with aryl,

[0643] (4) C1-C6-alkyl substituted with heterocyclyl, and

[0644] (5) C1-C6-alkyl substituted with heteroaryl;

[0645] In another embodiment, the present invention provides compounds of formula XVII: 70

[0646] or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of 71 72 73 74 75

[0647] Wherein

[0648] R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

[0649] In one aspect, the invention provides a method of inhibiting a deacetylase enzyme in a gram-negative bacteria, thereby affecting bacterial growth, comprising administering to a patient in need of such inhibition a compound of formula I.

[0650] In another aspect, the invention provides a method of inhibiting LpxC, thereby modulating the virulence of a bacterial infection, comprising administering to a patient in need of such inhibition a compound of formula I.

[0651] In some embodiments of the method of inhibiting LpxC using a compound of formula I, the IC50 value of the compound is less than or equal to 10 &mgr;M with respect to LpxC. In other such embodiments, the IC50 value is less than or equal to 1 &mgr;M, is less than or equal to 0.1 &mgr;M, is less than or equal to 0.050 &mgr;M, is less than or equal to 0.030 &mgr;M, is less than or equal to 0.025 &mgr;M, or is less than or equal to 0.010 &mgr;M.

[0652] In one aspect of the invention, methods for treating a subject comprising administering to the subject an antibacterially effective amount of a compound of formula I, together with a pharmaceutically acceptable carrier is provided. In a preferred embodiment of the method of treatment, the subject is a mammal and some embodiments, a human.

[0653] In another aspect, the invention provides a method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermnentative gram-negative bacteria. In a preferred embodiment of the method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermentative gram-negative bacteria, the gram-negative bacteria are selected from the group consisting of Pseudomonas aeruginosa, Stenotrophomonas maltophila, Burkholderia cepacia, Alcaligenes xylosoxidans, Acinetobacter, Enterobacteriaceae, Haemophilus, Neisseria species.

[0654] In another embodiment, the invention provides a method of administering an inhibitory amount of a compound of formula I to gram-negative bacteria, such as Enterobacteriaceae that is selected from the group consisting of organisms such as Serratia, Proteus, Klebsiella, Enterobacter, Citrobacter, Salmonella, Providencia, Morganella, Cedecea, and Edwardsiella species and Escherichia coli.

[0655] Another embodiment of the invention provides a pharmaceutical composition comprising an effective amount of a compound of Formula I with a pharmaceutically acceptable carrier thereof.

[0656] Pharmaceutical formnulations according to the present invention are provided which include any of the compounds described above in combination with a pharmaceutically acceptable carrier.

[0657] Another embodiment of the invention provides a method of co-administering the compound of formula I with other therapeutic agents that are selected for their particular usefulness against the condition that is being treated.

[0658] For example, the compound of formula I is useful in combination with other anti-bacterial agents. The compound of formula I augments the sensitivity of gram-negative bacteria to existing classes of antibacterials. Combinations of the presently disclosed compounds with other anti-bacterial agents are within the scope of the invention. Such anti-bacterial agents include, but are not limited to, erythromycin, rifampicin, Nalidixic acid, carbenicillin, bacitracin, cycloserine, fosfomycin, and vancomycin.

[0659] A further aspect of the invention is the use of LpxC inhibitors for the treatment of an infection, particularly a bacterial infection. A bacterial infection treated with the compounds of the invention can be a primary infection or a co-infection caused by a species of bacteria and one or more additional infectious agents selected from the group consisting of bacteria, virus, parasite and fungus.

[0660] The term “treating”, as used herein, refers to reversing, alleviating, inhibiting the progress of, or preventing the disorder or condition to which such term applies, or one or more symptoms of such disorder or condition. The term “treatment”, as used herein, refers to the act of treating, as “treating” is defined immediately above.

[0661] The compounds of the invention can be used for treating conditions caused by the bacterial production of endotoxin and, in particular, by gram-negative bacteria and bacteria that use LpxC in the biosynthesis of lipopolysaccharide (LPS) or endotoxin.

[0662] The compounds of the invention also are useful in the conditions that are caused or exacerbated by the bacterial production of lipid A and LPS or endotoxin, such as sepsis, septic shock, systemic inflammation, localized inflammation, chronic obstructive pulmonary disease (COPD) and acute exacerbations of chronic bronchitis (AECB). For these conditions, treatment includes the administration of a compound of the invention, or a combination of compounds of the invention, optionally with a second agent wherein the second agent is a second antibacterial agent or a second non-antibacterial agent.

[0663] For sepsis, septic shock, systemic inflammation, localized inflammation, chronic obstructive pulmonary disease (COPD) and acute exacerbations of chronic bronchitis (AECB), preferred second non-antibacterial agents include antiendotoxins including endotoxin receptor-binding antibodies, endotoxin-binding antibodies, antiCD14-binding protein antibodies antilipopolysaccharide-binding protein antibodies and tyrosine kinase inhibitors.

[0664] In treatment of serious or chronic respiratory tract infections, the compounds of the present invention may also be used with second non-antibacterial agents administered via inhalation. Preferred non-antibacterial agents used in this treatment include anti-inflammatory steroids, non-steroidal anti-inflammatory agents, bronchiodilators, mucolytics, anti-asthma therapeutics and lung fluid surfactants. In particular, the non-antibacterial agent may be selected from a group consisting of albuterol, salbuterol, budesonide, beclomethasone, dexamethasone, nedocromil, beclomethasone, fluticasone, flunisolide, triamcinolone, ibuprofin, rofecoxib, naproxen, celecoxib, nedocromil, ipratropium, metaproterenol, pirbuterol, salneterol, bronchiodilators, mucolytics, calfactant, beractant, poractant alfa, surfaxin and pulmozyme (also called domase alfa).

[0665] The compounds of the invention can be used, alone or in combination with a second antibacterial agent for the treatment of a serious or chronic respiratory tract infection including serious lung and nosocomial infections such as those caused by Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Prbteus mirabilis, Serratia marcescens, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter calcoaceticus, Alcaligenes xylosoxidans, Flavobacterium meningosepticum, Providencia stuartii and Citrobacter freundi, community lung infections such as those caused by Haemophilus Influenzae, Legionella species, Moraxella catarrhalis, Branhamella catarrhalis, Enterobacter species, Acinetobacter species, Klebsiella species, and Proteus species, and infections caused by other bacterial species such as Neisseria species, Shigella species, Salmonella species, Helicobacter pylori, Vibrionaceae and Bordetella species as well as the infections is caused by a Brucella species, Francisella tularensis and/or Yersinia Pestis.

[0666] When used for treating Gram-negative bacteria, the compounds of the present invention can be used to sensitize gram-negative bacteria to the effects of a second agent.

[0667] When the compounds of the present invention are used in combination with a second antibacterial agent, non-limiting examples of antibacterial agents may be selected from the following groups:

[0668] (1) Macrolides or ketolides such as erythromycin, azithromycin, clarithromycin and telithromycin;

[0669] (2) Beta-lactams including penicillin, cephalosporin, and carbapenems such as carbapenem, imipenem, and meropenem;

[0670] (3) Monobactams such as penicillin G, penicillin V, methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin, ampicillin, amoxicillin, carbenicillin, ticarcillin, mezlocillin, piperacillin, azlocillin, temocillin, cepalothin, cephapirin, cephradine, cephaloridine, cefazolin, cefamandole, cefuroxime, cephalexin, cefprozil, cefaclor, loracarbef, cefoxitin, cefinetazole, cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, ceftazidime, cefixime, cefpodoxime, ceftibuten, cefdinir, cefpirome, cefepime, and astreonam;

[0671] (4) Quinolones such as nalidixic acid, oxolinic acid, norfloxacin, pefloxacin, enoxacin, ofloxacin, levofloxacin, ciprofloxacin, temafloxacin, lomefloxacin, fleroxacin, grepafloxacin, sparfloxacin, trovafloxacin, clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, ganefloxacin, gemifloxacin and pazufloxacin;

[0672] (5) Antibacterial sulfonanmides and antibacterial sulphanilamides, including para-aminobenzoic acid, sulfadiazine, sulfisoxazole, sulfamethoxazole and sulfathalidine;

[0673] (6) Aminoglycosides such as streptomycin, neomycin, kanamycin, paromycin, gentamicin, tobramycin, amikacin, netilmicin, spectinomycin, sisomicin, dibekalin and isepamicin;

[0674] (7) Tetracyclines such as tetracycline, chlortetracycline, demeclocycline, minocycline, oxytetracycline, methacycline, doxycycline;

[0675] (8) Rifamycins such as rifampicin (also called rifampin), rifapentine, rifabutin, bezoxazinorifamycin and rifaximin;

[0676] (9) Lincosamides such as lincomycin and clindamycin;

[0677] (10) Glycopeptides such as vancomycin and teicoplanin;

[0678] (11) Streptogramins such as quinupristin and daflopristin;

[0679] (12) Oxazolidinones such as linezolid;

[0680] (13) Polymyxin, colistin and colymycin;

[0681] (14) Trimethoprim and bacitracin.

[0682] The second antibacterial agent may be administered in combination with the compounds of the present inventions wherein the second antibacterial agent is administered prior to, simultaneously, or after the compound or compounds of the present invention. When simultaneous administration of a compound of the invention with a second agent is desired and the route of administration is the same, then a compound of the invention may be formulated with a second agent into the same dosage form. An example of a dosage form containing a compound of the invention and a second agent is a tablet or a capsule.

[0683] When used for treating a serious or chronic respiratory tract infections, the compounds of the invention may be used alone or in combination with a second antibacterial agent administered via inhalation. In the case of inhalation, a preferred second antibacterial agent is selected from a group consisting of tobramycin, gentamicin, aztreonam, ciprofloxacin, polymyxin, colistin, colymycin, azithromycin and clarithromycin.

[0684] Pharmaceutical Compositions

[0685] Pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers. As used herein, the term “pharmaceutically acceptable carrier” means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials that can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, or as an oral or nasal spray, or a liquid aerosol or dry powder formulation for inhalation.

[0686] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

[0687] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables.

[0688] The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

[0689] In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form may be accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations may also be prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues.

[0690] Compositions for rectal or vaginal administration are preferably suppositories that can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.

[0691] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, acetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.

[0692] Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

[0693] The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes.

[0694] Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

[0695] The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes.

[0696] Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulations, ear drops, and the like arealso contemplated as being within the scope of this invention.

[0697] The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

[0698] Compositions of the invention may also be formulated for delivery as a liquid aerosol or inhalable dry powder. Liquid aerosol formulations may be nebulized predominantly into particle sizes that can be delivered to the terminal and respiratory bronchioles where bacteria reside in patients with bronchial infections, such as chronic bronchitis and pneumonia. Pathogenic bacteria are commonly present throughout airways down to bronchi, bronchioli and lung parenchema, particularly in terminal and respiratory bronchioles. During exacerbation of infection, bacteria can also be present in alveoli. Liquid aerosol and inhalable dry powder formulations are preferably delivered throughout the endobronchial tree to the terminal bronchioles and eventually to the parenchymal tissue.

[0699] Aerosolized formulations of the invention may be delivered using an aerosol forming device, such as a jet, vibrating porous plate or ultrasonic nebulizer, preferably selected to allow the formation of a aerosol particles having with a mass medium average diameter predominantly between 1 to 5 &mgr;m. Further, the formulation preferably has balanced osmolarity ionic strength and chloride concentration, and the smallest aerosolizable volume able to deliver effective dose of the compounds of the invention to the site of the infection. Additionally, the aerosolized formulation preferably does not impair negatively the functionality of the airways and does not cause undesirable side effects.

[0700] Aerosolization devices suitable for administration of aerosol formulations of the invention include, for example, jet, vibrating porous plate, ultrasonic nebulizers and energized dry powder inhalers, that are able to nebulize the formulation of the invention into aerosol particle size predominantly in the size range from 1-5 pm. Predominantly in this application means that at least 70% but preferably more than 90% of all generated aerosol particles are 1 to 5 &mgr;m range. A jet nebulizer works by air pressure to break a liquid solution into aerosol droplets. Vibrating porous plate nebulizers work by using a sonic vacuum produced by a rapidly vibrating porous plate to extrude a solvent droplet through a porous plate. An ultrasonic nebulizer works by a piezoelectric crystal that shears a liquid into small aerosol droplets. A variety of suitable devices are available, including, for example, AeroNeb and AeroDose vibrating porous plate nebulizers (AeroGen, Inc., Sunnyvale, Calif.), Sidestream7 nebulizers (Medic-Aid Ltd., West Sussex, England), Pari LC7 and Pari LC Star7 jet nebulizers (Pari Respiratory Equipment, Inc., Richmond, Va.), and Aerosonic (DeVilbiss Medizinische Produkte (Deutschland) GmbH, Heiden, Germany) and UltraAire7 (Omron Healthcare, Inc., Vernon Hills, Ill.) ultrasonic nebulizers.

[0701] Compounds of the invention may also be formulated for use as topical powders and sprays that can contain, in addition to the compounds of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons.

[0702] Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel.

[0703] According to the methods of treatment of the present invention, bacterial infections are treated or prevented in a patient such as a human or lower mammal by administering to the patient a therapeutically effective amount of a compound of the invention, in such amounts and for such time as is necessary to achieve the desired result. By a “therapeutically effective amount” of a compound of the invention is meant a sufficient amount of the compound to treat bacterial infections, at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts.

[0704] The total daily dose of the compounds of this invention administered to a human or other mammal in single or in divided doses can be in amounts, for example, from 0.01 to 50 mg/kg body weight or more usually from 0.1 to 25 mg/kg body weight. Single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. In general, treatment regimens according to the present invention comprise administration to a patient in need of such treatment from about 10 mg to about 2000 mg of the compound(s) of this invention per day in single or multiple doses.

[0705] Methods of formulation are well known in the art and are disclosed, for example, in Remington: The Science and Practice of Pharmacy, Mack Publishing Company, Easton, Pa., 19th Edition (1995). Pharmaceutical compositions for use in thepresent invention can be in the form of sterile, non-pyrogenic liquid solutions or suspensions, coated capsules, suppositories, lyophilized powders, transdermal patches or other forms known in the art.

[0706] A “kit” as used in the instant application includes a container for containing the pharmaceutical compositions and may also include divided containers such as a divided bottle or a divided foil packet. The container can be in any conventional shape or form as known in the art that is made of a pharmaceutically acceptable material, for example a paper or cardboard box, a glass or plastic bottle or jar, a resealable bag (for example, to hold a “refill” of tablets for placement into a different container), or a blister pack with individual doses for pressing out of the pack according to a therapeutic schedule. The container employed can depend on the exact dosage form involved, for example a conventional cardboard box would not generally be used to hold a liquid suspension. It is feasible that more than one container can be used together in a single package to market a single dosage form. For example, tablets may be contained in a bottle that is in turn contained within a box.

[0707] An example of such a kit is a so-called blister pack. Blister packs are well known in the packaging industry and are being widely used for the packaging of pharmaceutical unit. dosage forms (tablets, capsules, and the like). Blister packs generally consist of a sheet of relatively stiff material covered with a foil of a preferably transparent plastic material. During the packaging process, recesses are formed in the plastic foil. The recesses have the size and shape of individual tablets or capsules to be packed or may have the size and shape to accommodate multiple tablets and/or capsules to be packed. Next, the tablets or capsules are placed in the recesses accordingly and the sheet of relatively stiff material is sealed against the plastic foil at the face of the foil that is opposite from the direction in which the recesses were formed. As a result, the tablets or capsules are individually sealed or collectively sealed, as desired, in the recesses between the plastic foil and the sheet. Preferably the strength of the sheet is such that the tablets or capsules can be removed from the blister pack by manually applying pressure on the recesses whereby an opening is formed in the sheet at the place of the recess. The tablet or capsule can then be removed via said opening.

[0708] It maybe desirable to provide a written memory aid, where the written memory aid is of the type containing information and/or instructions for the physician, pharmacist or other health care provider, or subject, e.g., in the form of numbers next to the tablets or capsules whereby the numbers correspond with the days of the regimen that the tablets or capsules so specified should be ingested or a card that contains the same type of information. Another example of such a memory aid is a calendar printed on the card e.g., as follows “First Week, Monday, Tuesday,”. . . etc . . . “Second Week, Monday, Tuesday, . . . ” etc. Other variations of memory aids will be readily apparent. A “daily dose” can be a single tablet or capsule or several tablets or capsules to be taken on a given day. When the kit contains separate compositions, a daily dose of one or more compositions of the kit can consist of one tablet or capsule while a daily dose of another one or more compositions of the kit can consist of several tablets or capsules.

[0709] Another specific embodiment of a kit is a dispenser designed to dispense the daily doses one at a time in the order of their intended use. Preferably, the dispenser is equipped with a memory-aid, so as to further facilitate compliance with the regimen. An example of such a memory-aid is a mechanical counter, that indicates the number of daily doses that has been dispensed. Another example of such a memory-aid is a battery-powered micro-chip memory coupled with a liquid crystal readout, or audible reminder signal that, for example, reads out the date that the last daily dose has been taken and/or reminds one when the next dose is to be taken.

[0710] The kits of the present invention may also include, in addition to LpxC inhibitors, one or more additional pharmaceutically active compounds. Preferably, the additional compound is another LpxC inhibitor or another compound useful to bacterial infections. The additional compounds may be administered in the same dosage form as the LpxC inhibitor or in different dosage forms. Likewise, the additional compounds can be administered at the same time as the LpxC inhibitor or at different times.

[0711] Compositions of the present compounds may also be used in combination with other known antibacterial agents of similar spectrum to (1) synergistically enhance treatment of severe Gram-negative infections covered by the spectrum of this compound or (2) add coverage in severe infections in which multiple organisms are suspected in which another agent of a different spectrum may be required in addition to this compound. Potential agents include members of the aminoglycosides, penicillins, cephalosporins, fluoroquinolones, macrolides, glycopeptides, lipopeptides and oxazolidinones. The treatment can involve administering a composition having both active agents or administration of the inventive compounds followed by or preceded by administration of an additional active antibacterial agent.

[0712] Characterization and Purification Methods

[0713] Referring to the examples that follow, compounds of the present invention were characterized by high performance liquid chromatography (HPLC) using a Waters Millenium chromatography system with a 2690 Separation Module (Milford, Mass.). The analytical columns were Alltima C-18 reversed phase, 4.6×250 mm from Alltech (Deerfield, Ill.). A gradient elution was used, typically starting with 5% acetonitrile/95% water and progressing to 100% acetonitrile over a period of 40 minutes. All solvents contained 0.1% trifluoroacetic acid (TFA). Compounds were detected by ultraviolet light (UV) absorption at either 220 or 254 nm. HPLC solvents were from Burdick and Jackson (Muskegan, Mich.), or Fisher Scientific (Pittsburg, Pa.). In some instances, purity was assessed by thin layer chromatography (TLC) using glass or plastic backed silica gel plates, such as, for example, Baker-Flex Silica Gel 1 B2-F flexible sheets. TLC results were readily detected visually under ultraviolet light, or by employing well known iodine vapor and other various staining techniques.

[0714] Mass spectrometric analysis was performed on one of two LCMS instruments: a Waters System. (Alliance HT HPLC and a Micromass ZQ mass spectrometer; Column: Eclipse XDB-C-18, 2.1×50 mm; solvent system: 5-95% (or 35-95%, or 65-95% or 95-95%) acetonitrile in water with 0.05%TFA; flow rate 0.8 mL/min; molecular weight range 500-1500; cone Voltage 20 V; column temperature 40° C.) or a Hewlett Packard System (Series 1100 HPLC; Column: Eclipse XDB-C18, 2.1×50 mm; solvent system: 1-95% acetonitrile in water with 0.05% TFA; flow rate 0.4 mL/min; molecular weight range 150-850; cone Voltage 50 V; column temperature 30° C). All masses are reported as those of the protonated parent ions.

[0715] GCMS analysis was performed on a Hewlet Packard instrument (HP6890 Series gas chromatograph with a Mass Selective Detector 5973; injector volume: 1 &mgr;L; initial column temperature: 50° C.; final column temperature: 250C; ramp time: 20 minutes; gas flow rate: 1 mL/min; column: 5% phenyl methyl siloxane, Model #HP 190915-443, dimensions: 30.0 m×25 m×0.25 m).

[0716] Nuclear magnetic resonance (NMR) analysis was performed with a Varian 300 Mhz NMR (Palo Alto, Calif.). The spectral reference was either TMS or the known chemical shift of the solvent. Some compound samples were run at elevated temperatures (e.g. 75° C.) to promote increased sample solubility.

[0717] The purity of some of the invention compounds was assessed by elemental analysis (Desert Analytics, Tuscon, Ariz.)

[0718] Melting points were determined on a Laboratory Devices Mel-Temp apparatus (Holliston, Mass.).

[0719] Preparative separations were carried out using a Flash 40 chromatography system and KP-Sil, 60A (Biotage, Charlottesville, Va.), or by flash column chromatography using silica gel (230-400 mesh) packing material, or by HPLC using a C-18 reversed phase column. Typical solvents employed for the Flash 40 Biotage system and flash column chromatography were dichloromethane, methanol, ethyl acetate, hexane, acetone, aqueous hydroxyamine and triethyl amine. Typical solvents employed for the reverse phase HPLC were varying concentrations of acetonitrile and water with 0.1% trifluoroacetic acid.

[0720] Compounds of the present invention can be readily synthesized using the methods described herein, or other methods, that are well known in the art. For example, the synthesis of hxdroxamic acids or similar scaffolds having a wide variety of substituents are comprehensively reviewed in Kline T, Andersen N H, Harwood E A, Bowman J, Malanda A, Endsley S, Erwin A L, Doyle M, Fong S, Harris A L, Mendelsohn B,. Mdluli K, Raetz C R, Stover C K, Witte P R, Yabannavar A, Zhu S., “Potent, novel in vitro inhibitors of the Pseudomonas aeruginosa deacetylase LpxC,” J. Med Chem 2002 July 4;45(14):3112-29; Patchett, A. A., Nargund, R., Chen, M.-H., Nishi, H. R., U. S. Pat. No. 5,925,659, 1999; Pirrung, M. C., Chau, J. H., “A Convenient Procedure for the Preparation of Amino Acid Hydrokamates from Esters,” J. Org. Chem. 1995, 60, 8084-8085; Nhu, K., Patel, D. V., “A New and Efficient Solid Phase Synthesis of Hydroxamic Acids,” J. Org. Chem. 1997, 62, 7088-7089; Patel, D., Nhu, K., “Methods for Solid-phase Synthesis of Hydroxylamine Compounds and Derivatives, and Combinatorial Libraries Thereof,” PCT WO 98/18754, 1998, Mellor, S. L., McGuire, C., Chan, W. C., “N-Fmoc-aminoxy-2-chlortrityl Polystyrene Resin: A Facile Solid-phase Methodology for the Synthesis of Hydroxamic Acids,” Tetrahedron Lett., 1997, 38, 3311-3314; Khan, S. I., Grinstaff, M. W., “A Facile and Convenient Solid-phase Procedure for Synthesizing Nucleoside Hydroxamic Acids,” Terahedron. Lett., 1998, 39, 8031-8034; Zhang, Y., Li, D., Houtman, J. C., Witiak, D. T., Seltzer, J., Bertics, P. J., Lauhon, C. T., “Design, Combinatorial Chemical Synthesis, and in vitro Characterization of Novel Urea Based Gelatinase Inhibitors,” Bioorg. Med. Chem. Lett., 1999, 9, 2823-2826; Ito, Y., Inubushi, Y., Zenbayashi, M., Tomita, S., Saegusa, T., “Synthetic Reactions by Complex Catalysts. XXXI, A Novel and Versatile Method of Heterocycle Synthesis,” J. Am Chem. Soc., 1973, 95, 4447-4448; Ito, Y., Ito, I., Hirao, T., Saegus, T., “Synthetic Reactions by Complex Catalysts XXXV,” Syn. Commun. 1974, 4, 97-103; Witte, H., Seliger, W., “Cyclische Imidsaurester aus Nitrilen und Aminoalkoholen,” Liebigs Ann. Chem, 1974, 996-1009; Pattenden, G., Thom. S. M., “Naturally Occurring Linear Fused Thiazoline-Thiazole Containing Metabolites: Total Synthesis of (−) Didehydromirabazole A, a Cytotoxic Alkaloid from Blue-Green Algae,” J. Chem. Soc. Perkin Trans 1, 1993, 1629-1636; Boyce, R. J., Mulqueen, G. C., Pattenden, G., “Total Synthesis of Thiangazole, A Novel Naturally Occurring HIV-1 Inhibitor from Polyangium sp.,” Tetrahedron, 1995, 51, 7321-7330; Galeotti, N., Plagnes, E., Jouin, P., “Synthesis of Peptidyl Aldehydes from Thiazolines,” Tetrahedron. Lett. 1997, 38, 2459-2462; Charette, A. B., Chua, P., “Mild Method for the Synthesis of Thiazolines from Secondary and Tertiary Amides,” J. Org. Chem., 1998, 63, 908-909; Bergeron, R. J., Wiegand, J., McManis, J. S., McCosar, B. H., Weimar, W. R., Brittenham, G. M., Smith, R. E., “Effects of C-4 Stereochemistry and C-4′ Hydroxylation on the Iron Clearing Efficiency and Toxicity of Desferrithiocin Analogues,” J. Med. Chem. 1999, 42, 2432-2440; Raman, P., Razavik H., Kelly, J. W., “Titanium (IV)-mediated Tandem Deprotection-cyclodehydration of Protected Cysteine N-Amides: Biomimetic Synthesis of Thiazoline- and Thiazole-containing Heterocycles,” Org. Lett., 2000, 2, 3289-3292; Fernandez, X., Fellous, R., Dunach, E., “Novel Synthesis of 2-Thioazolines,” Tetrahedron Lett., 2000, 41, 3381-3384. Wipf, P., Miller, C. P., Venkatraman, S., Fritch, P., “C. Thiolysis of Oxazolinenes: A New, Selective Method for the Direct Conversion of Peptide Oxazolines into Thiazolines,” Tetrahedron Lett., 1995, 36, 6395-6398, which are incorporated herein by reference.

[0721] The synthesis of other non-hydroxamates compounds or more generally zinc binding groups are reviewed in Pirrung, M. C., Tumey, L. N., Raetz, C. R. H., Jackman, J. E., Snehalatha, K., McClerren, A. L., Fierke, C. A., Gantt, S. L., Rusche, K. M., “Inhibition of the Antibacterial Target UDP-(3-O-acyl)-N-acetylglucosamine Deacetylase (LpxC): Isoxazoline Zinc Amidase Inhibitors Bearing Diverse Metal Binding Groups,” Journal of Medicinal Chemistry (2002), 45(19), 4359-4370; Jackman, J. E., Fierke, C. A., Tumey, L. N., Pirrung, M., Uchiyama, T., Tahir, S. H., Hindsgaul, O., Raetz, C. R. H., “Antibacterial agents that target lipid A biosynthesis in gram-negative bacteria: inhibition of diverse UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs,” Journal of Biological Chemistry (2000), 275(15), 11002-11009; Brooks, C. D. W., Summers, J. B., “Modulators of Leukotriene Biosynthesis and Receptor Activation,” Journal of Medicinal Chemistry (1996), 39(14), 2629-2654; Jeng, A. Y., De Lombaert, S., “Endothelin converting enzyme inhibitors,” Current Pharmaceutical Design (1997), 3(6), 597-614; Zask, A., Levin, J. I., Killar, L. M., Skotnicki, J. S., “Inhibition of matrix metalloproteinases: structure based design,” Current Pharmaceutical Design (1996), 2(6), 624-661; Skotnicki, J. S., DiGrandi, M. J., Levin, J. I., Chemical and Screening Sciences, Wyeth Research, New York, N.Y., USA. Current Opinion in Drug Discovery & Development (2003), 6(5), 742-759.

[0722] The foregoing may be better understood by reference to the following examples, that are presented for illustration and not to limit the scope of the inventive concepts.

EXAMPLES

[0723] The following are abbreviations used in the examples: 1 AcOH: Acetic acid aq: Aqueous ATP: Adenosine triphosphate Boc: tert-butoxycarbonyl Boc-Thr(OBn)-OH 3-(R)-Benzyloxy-2-(S)-tert-butoxycarbonylamino- butyric acid. DAP or Dap: Diaminopropionate DCM: 4-(Dicyanomethylene)-2-methyl-6- (4-dimethylaminostyryl)-4H-pyran DEAD: Diethyl azodicarboxylate DIEA: Diisopropylethylamine DME: 1,2-dimethoxyethane DMF: N,N-Dimethylformamide DMSO: Dimethyl sulfoxide DPPA: Diphenyl phosphoryl azide Et3N: Triethylamine EDC: N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide EDCI: 1-(3-dimethylaminopropyl)3-ethylcarbodiimide EtOAc: Ethyl acetate EtOH: Ethanol Fmoc: 9-fluorenylmethoxycarbonyl Gly-OH: glycine HATU: O-(7-azabenzotriaazol-1-yl)-N,N,N′N′= tetramethyluronium hexafluorophophate HBTU: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate Hex: hexane HOBt: butyl alcohol HOBT: 1-Hydroxybenzotriazole HPLC: High Pressure Liquid Chromatography IC50 value: The concentration of an inhibitor that causes a 50% reduction in a measured activity. iPrOH: Isopropanol LC/MS: Liquid Chromatography/Mass Spectrometry LRMS: Low Resolution Mass Spectrometry MeOH: Methanol NaOMe: sodium methoxide nm: Nanometer NMP: N-Methylpyrrolidone PPh3: triphenyl phosphine RP-HPLC: Reversed-phase high-pressure liquid chromatography RT: Room temperature sat: Saturated TEA: Triethylamine TFA: Trifluoroacetic acid THF: Tetrahydrofuran Thr: Threonine TLC: Thin Layer Chromatography Trt-Br: Tert-butyl bromide

[0724] Nomenclature for the Example compounds was provided using ACD Name version 5.07 software (Nov. 14, 2001) available from Advanced Chemistry Development, Inc. Some of the compounds and starting materials were named using standard IUPAC nomenclature.

SYNTHESIS OD N-AROYL THREONINE ANALOGUES AND FORMATION OF HYDROXAMATE

Example 1

[0725] Synthesis of 3-bromo4-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide (3) 2 76 77 78 Reagent MW Eq. g/ml mmol Benzoic acid (1) 219.02 1.0 2.152 g 9.83 L-Thr-OMe—HCl 169.61 1.2 1.968 g 11.6 EDCI 191.71 1.2 2.218 g 11.6 HOBt 135.13 1.1 1.410 g 10.4 DIEA 129.25 4.0 6.8 mL 39.0 DMF 60 mL

[0726] Preparation of (2S,3R)-2-(3-bromo-4-fluoro-benzoylamino)-3-hydroxy-butyric Acid Methyl Ester (2)

[0727] Diisopropylethylamine (6.8 mL, 39.0 mmol) was added to a stirred solution of 3-bromo-4-fluorobenzoic acid 1 (2.152 g, 9.83 mmol), L-threonine methyl ester hydrochloride (1.968 g, 11.6 mmol), EDCI (2.218 g, 11.6 mmol) and HOBt (1.410 g, 10.4 mmol) in anhydrous DMF (60 mL) at 0° C. under N2. The solution was stirred at 0° C. for 1 h and at room temperature for 20 h. The solution was diluted with EtOAc (300 mL) and washed with 1.0 M HCl (2×80 mL), saturated NaHCO3 (2×80 mL), H2O (4×80 mL), dried over MgSO4, filtered and concentrated in vacuo to give a colorless syrup which solidified on standing to afford 3.280 g (100%) of (2S,3R)-2-(3-bromo-4-fluoro-benzoylamino)-3-hydroxy-butyric acid methyl ester 2 as a white solid, mp 73-74° C. MS(ES+) m/z 333.9 (C12H13BrFNO4+H requires 334.00).

[0728] Preparation of 3-bromo-4-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide (3) 79

[0729] To a solution of hydroxylamine hydrochloride (66 mg, 0.95 mmol) in anhydrous MeOH (2.0 mL) at 0° C. under N2 atmosphere was added sodium methoxide (25 wt % in MeOH, 360 mg, 1.67 mmol). A precipitate formed immediately and the cloudy white solution was stirred for 10 minutes at 0° C. A solution of methyl (2S,3R)-2-[(3-bromo-4-fluorophenyl)carbonylamino]-3-hydroxybutanoate (2) (284 mg, 0.850 mmol) in MeOH (2.0 mL) was added and the reaction stirred 2 h at 0° C. and then warmed gradually to room temperature overnight (17 h total). Aqueous 1.0 M HCl (10 mL) was added and the solution extracted with 4:1 chloroform/isopropyl alcohol (4×20 mL). The organic layers were combined, dried over Na2SO4 and concentrated to give a pink foam. The crude solid was triturated with diethyl ether (2×8 mL) and dried in vacuo to give 3-bromo4-fluoro-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 3 as a white foam: mp 152-153° C. Rf (10:1 CH2Cl2/MeOH on silica gel)=0.53.

Preparation of Hydroxamates

Example 2

[0730] Synthesis of 4-benzoyl-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 80

[0731] Procedure:

[0732] To a solution of hydroxylamine hydrochloride (121 mg, 1.74 mmol) in anhydrous MeOH (2.0 mL) at 0° C. under N2 atmosphere was added sodium methoxide (25 wt % in MeOH, 680 mg, 3.14 mmol). A precipitate was immediately observed and the cloudy white solution was stirred for 10 minutes at 0° C. A solution of methyl (2S,3R)-3-hydroxy-2-{[4-(phenylcarbonyl)phenyl]carbonylamino}butanoate (1) (534 mg, 1.56 mmol) in MeOH (3.0 nL) was added and the reaction stirred 3 h at 0° C., then warmed gradually to ambient temperature overnight (18 h total). Aqueous 0.5 M HCl (20 mL) was added and the solution extracted with 5:1 chloroform/isopropyl alcohol (4×40 mL). The organic layers were combined, dried over Na2SO4 and concentrated to give an orange foam. Purification by silica gel chromatography (increasing eluant polarity from 30:1 CH2Cl2/MeOH to 15:1 CH2Cl2/MeOH) afforded 228 mg (43%) of 4-benzoyl-N-{1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide.

Example 3

[0733] Synthesis of (2R, 3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carbohydroxamic acid

[0734] Preparafion of ((2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl)}pyrrolidin-2-yl)-N-(phenylmethoxy)carboxamide (2) 81

[0735] Procedure:

[0736] To a solution of (2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carboxylic acid (1) (405 mg, 1.27 mmol), benzylhydroxylamine hydrochloride (243 mg, 1.52 mmol), HATU (556 mg, 1.46 mmol), and HOBt (178 mg, 1.32 mmol) in DMF (10 mL) at 0° C. was added diisopropylethylamine (710 &mgr;L, 4.07 mmol) with stirring. The cooling bath was removed after one hour and the reaction mixture stirred at ambient temperature for 18 h and then diluted with EtOAc (200 mL). The organic layer was washed with 1.0 M HCl (2×60 mL), sat. NaHCO3 (2×60 mL) and H2O (5×60 mL), dried over MgSO4 and concentrated to give 493 mg (92%) of ((2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-N-(phenylmethoxy)carboxamide (2), a colorless oil that slowly crystallized upon standing. Rf (25:1 CH2Cl2/MeOH)=0.35.

[0737] Prepartion of (2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carbohydroxamic acid (2) 82

[0738] Procedure:

[0739] To a solution of ((2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-N-(phenylmethoxy)carboxamide (1) (143 mg, 0.337 mmol) in EtOH (10 mL) was added 20% Pd(OH)2/C (50 mg). The solution was purged with hydrogen gas (approx. 0.5 L from a 1 L balloon) and then stirred under an atmosphere of H2 (balloon pressure). TLC analysis showed no starting material after one hour. The solution was diluted with EtOAc (10 mL) and filtered through celite, washing with 20:1 EtOAc/EtOH (50 mL). The solution was concentrated and dried in vacuo to afford 90 mg (80%) of (2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidine-2-carbohydroxamic acid (2) as a sticky white foam: mp 64-65° C. Rf (10: 1 CH2Cl2/MeOH)=0.29.

Synthesis of N-Benzyl Threonine Analogues by Reductive Amination

Example 4

[0740] Synthesis of (2S,3R-3-hydroxy-2-{[(4-phenylphenyl)methyl]amino}butanehydroxamic acid (3). 3 83 84 85 Reagent MW Eq. g/ml mmol 4-biphenylcarboxaldehyde 182.22 1.0 1.104 g 6.06 L-Thr-OMe—HCl 169.61 1.0 1.030 g 6.07 NaBH(OAc)3 211.94 1.4 1.800 g 8.49 Et3N 101.19 2.0 1.70 mL 12.1 THF 25 mL

[0741] Triethylamine (1.70 mL, 12.1 mmol) was added to a stirred suspension of L-threonine methyl ester hydrochloride (1.030 g, 6.07 mmol) and 4-biphenylcarboxaldehyde (1.104 g, 6.06 mmol) in THF (25 mL). After 20 min, NaBH(OAc)3 was added and the suspension stirred for 20 h. The reaction was monitored by TLC (50:1 DCM/MeOH, Rf=0.4). The reaction mixture was quenched with saturated NaHCO3 (50 mL), extracted with EtOAc (2×120 mL), dried over MgSO4, filtered and concentrated to give a yellow oil. Purification by silica gel chromatography (150:1 DCM/MeOH) afforded 1.220 g (67% yield, 98% pure) of (2S,3R)-2-[(biphenyl-4-ylmethyl)-amino]-3-hydroxy-butyric acid methyl ester 2 as a pale yellow oil.

[0742] HPLC (260 nm, 34 min run) 14.2 min; LRMS(ES+) m/z 299.9 (C18H21NO3+H requires 300.10). Compound 3 was then formed by the addition of NH2OH in MeOH/NaOMe at 0° C., warming to ambient temparture of the period of several hours. LCMS MH+301.15.

[0743] General Methods for Making Phenyl-benzoic Acids and Phenyl-benzoate Esters(see Example 5 Below) 86

[0744] Suzuki Procedures Using Pd(dppf)Cl2-DCM Catalyst and a THF/H2O Mixture 4 87 Reagent MW EQ g/ml mmol BromoArene #1 ˜300 1 100 mg ˜0.33 Boromc Acid #2 — 1.2 — ˜0.40 Na2CO3 105.99 3 104 m ˜0.99 Pd(dppf)Cl2 816.63 0.1-0.2 27-54 mg ˜0.033-0.066 THF (3) (sparged 0.75 ml with argon for 5 min.) water (1) (sparged 0.25 ml with argon for 5 min.)

[0745] Standard Procedure

[0746] 1 eq aryl halide (1) was added to 1.2 eq. (2) and Pd(dppf)Cl2 in Th, followed by addition of water and stirred 8 hours at RT. Upon completion (usually over night), the reactions are diluted with ethyl acetate (5-10 ml) and water (1 ml). The organic layer is separated and washed with NaHCO3 (2×3 ml), water (1×3 ml), brine (1×3 ml), dried with Na2SO4, filtered and concentrated in an 8 ml glass vial. The residue is dissolved in DMSO and injected on a preparatory HPLC reverse phase column to afford >80% yield.

[0747] Suzuki Procedures Using Pd(dppf)Cl-DCM Catalyst and DMF Solvent 5 88 Reagent MW EQ g/ml mmol BromoArene #1 ˜500 1 20 mg ˜0.04 Boronic Acid #2 ˜200 2 ˜14 mg ˜0.08 Pd(dppf)Cl2 816.63 0.25 10 mg ˜0.01-0.02 TEA 101.19 5 28 &mgr;L ˜0.2 DMF (dry & sparged 0.5 ml with argon for 5 min.)

[0748] Standard Procedure

[0749] The haloarene 1 and boronic acid 2 were weighed out and placed in the reaction flask. The DMF was sparged with argon for 5-10 minutes, followed by TEA addition, and the reaction was lightly bubbled with argon. The solid Pd(dppf)Cl2 catalyst was added in one portion. The vial was flushed with argon, capped tight and stirred or shaken at ˜80° C. Upon reaching completion (over night), the reaction was filtered and injected on a preparatory HPLC reverse phase column (80% yield).

Synthesis of Methyl DAP Analogues

Example 5

[0750] 3-(R)-Amino-2-(S)-[(4′-ethyl-biphenyl-4-carbonyl)-amino]-butyl-hydroxamic acid (8) 89

[0751] Preparation of N-triphenylmethyl allo-threonine Methyl Ester (2). 6 90 Reagent MW EQ g/ml mmol H-allo-Thr-OMe.HCl (1) 169.7 1.2 2.0 g 12.0 Trt-Br 323.24 1.0 3.23 g 10.0 DIEA 129.25 3.0 5.2 ml 30.0 CHCl3 (dry) 100 ml

[0752] For similar-procedures see: Righi, P.; Scardovi, N.; Marotta, E.; ten Holte, P.; Zwanenburg, B. Organic Letters 2002, 4(4), 497-500.

[0753] A solution of trityl bromide (3.2 g, 10.0 mmol) in CHCl3 (40 ml) was added dropwise to a stirred solution of allo-threonine methyl ester HCl salt (1) (2.0 g, 12.0 mmol) and DIEA (5.2 ml, 30.0 mmol) in CHCl3 (60 ml) at rt under N2. The reaction could be followed by TLC eluting with EtOAc/Hex (40:60) (Rf=0.3). After stirring 12 h, the reaction was concentrated to a brown oil. The crude product was diluted with EtOAc (170 ml) and washed with 0.2 N citric acid (2×50 ml), water (2×50 ml), brine (50 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to yield 3.73 g (85% yield, 95% pure) of a yellow solid.

[0754] HPLC(220 nm, 41 min. run) 30.90 min.; HPLC(220 nm, 17 min. run) 14.86 min.; LCMS: LC(214 nm) 3.06 min., MS(ES+) m/z 376.2 (C24H25NO3 +H requires 376.18).

[0755] Preparation of 3-(R)-Azido-2-(S)-(trityl-amino)-butyric Acid Methyl Ester (3). 7 91 Reagent MW Eq. g/ml mmol Trt-allo-Thr-OMe (2) 375.46 1.0 4.08 g 10.88 PPh3 262.29 1.0 2.85 g 10.88 DEAD (neat) 174.16 1.6 2.93 ml 17.82 DPPA 275.7 2.7 6.40 ml 29.7 THF (dry) 50 ml

[0756] For similar procedures see: Matsuda, A.; Yasuoka, J.; Sasaki, T.; Ueda, T. J.Med.Chem. 1991, 34, 999-1002.

[0757] A solution of pure DEAD (2.9 ml, 17.8 mmol) in THF (5 ml) was added slowly dropwise to a stirred solution of trt-allo-threonine methyl ester (2) (4. 1 g, 10.9 mmol) and PPh3 (2.9 g, 10.9 mmol) in THF (40 ml) at 0° C. under N2. After 3 min., a solution of DPPA (6.4 ml, 29.7 mmol) in THF (5 ml) was added to the orange-yellow reaction solution at 0° C. After 1 h, the reaction was allowed to warm to rt. After 40h, the reaction had reached completion by TLC (Hexane/DCM/EtOAc (64:20:16) (Rf=0.6)) and LCMS. The yellow solution was concentrated to give 18 g of crude material that was purified by column chromatography eluting with Hexane/EtOAc (88:12) giving 3.5 g of 70% pure product after evaporation. The product was purified again (to remove trityl alcohol and a crotyl side-product formed during the reaction by elimination) by column chromatography eluting with Hexane/DCM/EtOAc (76:20:4) giving 1.65 g (38% yield) of a pale yellow oil after concentration and drying in vacuo. Note that the trityl protecting group would hydrolyze when exposed to TFA while running the sample on HPLC.

[0758] Alternately, the reaction could be carried out in dry DCM. A reaction using 5.44 g (14.5 mmol) of trt-allo-threonine methyl ester (2) in DCM (100 ml) with PPh3 (3.8 g, 14.5 mmol), pure DEAD (3.4 ml, 21.8 mmol) in DCM (5 ml) and DPPA (6.3 ml, 24.0 mmol) in DCM (10 ml) were combined following the procedure above. After 3 days, the reaction did not progress further by TLC and LCMS. After the same work up, 2.97 g of the product was obtained in 51% yield.

[0759] HPLC(220 nm, 41 min. run) 40.5 min.; HPLC(220 nm, 17 min. run) 16.32 min.; LCMS: LC(214 nm) 3.7 min., MS(ES+) m/z 401.2 (C24H25N3O2+H requires 401.15).

[0760] Preparation of 2-(S)-Amino-3-(R)-azido-butyric acid methyl ester HCl salt (4). 8 92 Reagent MW EQ g/ml mmol Trt-Azido-Thr-OMe (3) 400.47 1.0 4.79 g 11.98 TFA 57 ml CHCl3 (dry) 3 ml

[0761] A solution of Trt-Azido-Thr-OMe (3) (4.8 g, 12.0 mmol) was dissolved in a 95% TFA/DCM solution (60 ml) at rt with stirring. After 2.5 h, the reaction was complete by LCMS. The bright yellow solution was diluted with 0.5 N aq. HCl (300 ml). The aqueous layer was extracted with DCM (2×30 ml) and then lyophilized to dryness. The white solid was dissolved in AcCN/water (50:50) (100 ml) and again lyophilized to dryness to produce a consistent powder and remove as much of the TFA as possible. The azido-Thr′product (4), 2.26 g (97% yield, 95% pure) of a white solid, was obtained as the HCl salt.

[0762] HPLC(220 nm, 41 min. run) 7.91 min.; HPLC(220 nm, 17 min.run) 3.36 min; LCMS: LC(214 nm) 0.48 min., MS(ES+) m/z 159.3 (C5H10N4O2+H requires 159.08).

[0763] Preparation of 3-(R)-Azido-2-(S-[(4′-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester (6). 9 93 94 Reagent MW EQ g/ml mmol Azido-Thr-OMe.HCl (4) 194.62 1.0 195 mg 1.0 Biphenyl Acid (5) 226.27 1.0 226 mg 1.0 HOBT 153 1.0 158 mg 1.0 EDC.HCl 191.17 1.3 249 mg 1.3 DIEA 129.25 2.5 0.44 ml 2.5 DCM (dry) 10 ml

[0764] A EDC.HCl (249 mg, 1.3 mmol) was added to a stirred colorless solution of azido-Thr-OMe.HCl (4) (195 mg, 1.0 mmol), HOBT (158 mg, 1.0 mmol), 4′-Ethyl-biphenyl-4-carboxylic acid (5) (226 mg, 1.0 mmol) and DIEA (0.44 ml, 2.5 mmol) in DCM (10 ml) at rt under N2. After 24 h, the reaction had reached completion by TLC (Hexane/EtOAc (60:40) (Rf=0.3)) and LCMS. The reaction was evaporated under reduced pressure to a brown tar. The crude product was dissolved in EtOAc (100 ml) and washed with 0.2N aq. HCl (2×50 ml), aq. sat. NaHCO3 (50 ml), brine (50 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to yield a crude brown solid. The crude material was further purified by column chromatography eluting with Hexane/EtOAc (70:30) giving 245 mg (67% yield) of pure product after evaporation and drying in vacuo.

[0765] HPLC(220 nn, 41 min. run) 33.87 min.; HPLC(220 nm, 17 min. run) 15.61 min; LCMS: LC(214 nm) 3.25 min., MS(ES+) m/z 367.2(C20H22N4O3 +H requires 367.17).

[0766] Preparation of 3-(R)-Amino-2-(S)-[(4′-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester (7). 10 95 96 Reagent MW EQ g/ml mmol Biphenyl Azido-Thr (6) 366.41 1.0 244 mg 0.67 10% Pd/C 200 mg H2 (gas) 12″ balloon MeOH (dry) 10 ml

[0767] A solution of biphenyl azido-Thr methyl ester (6) (244 mg, 0.67 mmol) in MeOH (10 ml) was made by sonicating until the milky precipitate cleared. After bubbling nitrogen through the reaction solution for 30 sec., 10% Pd/C was added in one portion. The reaction was stirred under nitrogen at RT. The reaction was exposed to aspirator vacuum to remove the nitrogen and then opened to the hydrogen gas at balloon pressure (˜1 atm). The reaction stirred for 3 h at which time the hydrogen was exchanged for nitrogen. The reaction was filtered through a pad of celite to remove the palladium. The celite pad was washed with MeOH (30 ml). The combined fractions of MeOH were evaporated under reduced pressure and dried in vacuo to give 225 mg (99% yield) of pure produce (7) as a white solid.

[0768] HPLC(220 nm, 17 min. run) 10.79 min.; LCMS: LC(214 nm) 2.21 min., MS(ES+) m/z 341.2 (C20H24N2O2+H requires 341.18).

[0769] Preparafion of 3-(R)-Amino-2-(S)-[(4′-ethyl-biphenyl-4-carbonyl)-amino]-butyl-hydroxamic acid (8) 11 97 98 Reagent MW EQ g/ml mmol Amino-Thr-OMe (7) 340.42 1.0 225 mg 0.66 H2NOH.HCl 69.49 10.0 460 mg 6.6 NaOMe 54.02 ˜12.0 ˜430 mg 7.92 MeOH (dry) 7 ml DCM (dry) 5 ml

[0770] To a stirred suspension of biphenyl-amino-Thr methyl ester (7) (225 mg, 0.6 mmol) and hydroxylamine HCl salt (460 mg, 6.6 mmol) in MeOH (7 ml) and DCM (5 ml) was added fresh solid NaOMe powder (430 mg, 7.92 mmol) in one portion. After strrring for 2 min. at rt under nitrogen, the pH of the reaction on wet pH paper was approximately 7-8. The suspension had change from larger particles of white solid to a finely-divided milky consistency. The pH of the reaction was checked after adding small portions of NaOMe (50-100 mg) and allowing 2 min. for the reaction to equilibrate. The pH of the reaction reached a stable 11-12 after the final portion of NaOMe was added (250 mg total). The reaction was initiated at pH 11 and proceeded quickly. After 30 min., the reaction reached 85% completion as determined by LCMS, and the reaction was placed in a −10° C. bath. The cold mixture filtered over fine filter paper on a Büchner funnel. The white residue was washed with MeOH (15 ml). The organic fractions were collected and concentrated under reduced pressure to give crude product (750 mg). The crude product (only one 150 mg portion) was dissolved in DMSO (1 ml), AcCN (100 &mgr;l) and water (100 &mgr;l ), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness. The product as the TFA salt was dissolved in AcCN/water (50:50) (5 ml), 1N aq. HCl (1 equivalent) and lyophilized again to give 11.5 mg of white powder as an HCl salt (23% yield).

[0771] HPLC(220 nm, 41 min. run) 19.31 min.; HPLC(220 nm, 17 min. run) 9.39 min; LCMS: LC(214 nm) 1.98 min., MS(ES+) m/z 342.2 (C19H23N3O3+H requires 342.17).

Synthesis of 4′Benzamide Biphenyl Threonine Hydroxamic Acid

Example 6

[0772] Biphenyl-4,4′-dicarboxylic acid 4′-[(3-Boc-amino-propyl)-amide] 4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide] (6), and

Example 7

[0773] Biphenyl-4,4′-dicarboxylic acid 4′-[(3-amino-propyl)-amide] 4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide] (7) 99

[0774] Synthesis of (2S,3R)-2-amino-3-(phenylmethoxys)-N-(phenylmethoxy)butanamide (1) 100

[0775] Procedure:

[0776] To a suspension of benzylhydroxylamine hydrochloride (8.310 g, 52.06 mmol), Boc-Thr(OBn)-OH (14.01 g, 45.28 mmol), EDCI (10.01 g, 52.21 mmol), and HOBt (6.90 g, 51.06 mmol) in CH2Cl2 (300 mL) at 0° C. was added diisopropylethylamine (28.3 mL, 162 mmol) with stirring. The cooling bath was removed after one hour and the reaction mixture stirred at ambient temperature for 20 h and was then diluted with Ch2Cl2 (300 mL). The organic layer was washed with 1.0 M HCl (2×200 mL), sat. NaHCO3 (2×200 mL) and brine (200 mL), dried over MgSO4 and concentrated to give 14.5 g of a white solid. The crude solid was treated with a solution of trifluoroacetic acid (90 riL) in CH2Cl2 (90 mL) and stirred for 2.5 h. The reaction mixture was concentrated by rotary evaporation and then diluted with CH2Cl2 (600 mL). The organic layer was washed with sat. NaHCO3 (2×200 mL), dried over MgSO4 and concentrated to give a dark orange oil. Purification by silica gel chromatography (50:1 CH2Cl2/MeOH) afforded (2S,3R)-2-amino-3-(phenylmethoxy)-N-(phenylmethoxy)butanamide (A) (8.9 g,) as a pale yellow oil. Rf(50:1 CH2Cl2/MeOH on silica gel)=0.2.

[0777] Preparation of (1S,2R)-4′-(2-benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acid (3). 12 Reagent MW Eq. g/mL mmol Amine (1) 314.38 1.0 0.944 g 3.00 Dicarboxylic acid (2) 242.23 1.9 1.360 g 5.61 BOP 442.3 1.5 2.007 g 4.54 DIEA 129.25 3.3  1.7 mL 9.76 DMF   200 mL

[0778] To a suspension of 4,4′-biphenyldicarboxylic acid 2 (1.360 g, 5.61 mmol) in DMF (180 mL) was added BOP (2.007 g, 4.54 mmol) and DIEA (1.7 mL, 9.8 mrmol). A solution of (IS,2R)-2-amino-3,N-bis-benzyloxy-butyramide 1 (944 mg, 3.00 mmol) in DMF (20 mL) was added and the reaction stirred for 18 h. The solution was diluted with EtOAc (250 mL) and washed with 1.0 M HCl (500 mL). The aqueous layer was extracted with EtOAc (250 mL) and the organic layers combined. The organic layer was washed with 1.0 M HCl (250 mL), dried over MgSO4, and concentrated to give a crude yellow solid. Purification by silica gel chromatography (60:1 CH2Cl2/MeOH) gave 210 mg (1S,2R)-4′-(2-benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acid 3. (13% yield) as a yellow solid. Rf=0.80 (10:1 CH2Cl2/MeOH); LRMS (ES+) m/z 539.1 (C32H30N2O6+H requires 539.22).

[0779] Preparation of biphenyl-4,4′-dicarboxylic acid 4′-[(3-(Boc)-amino-propyl)-amide]4-[(2R)-benzyloxy-(1S)-benzyloxycarbamoyl-propyl)-amide] (5). 13 Reagent MW Eq. g/mL mmol Biphenylcarboxylic acid (3) 538.59 1.0 0.200 g 0.371 Amine (4) 174.24 1.1 0.071 g 0.407 EDCI 191.71 1.1 0.078 g 0.407 HOBt 135.13 1.0 0.052 g 0.385 DIEA 129.25 2.7   180 &mgr;L 1.0 DMF    2 mL

[0780] To a solution of biphenylcarboxylic acid 3 (200 mg, 0.371 mmol), EDCI (78 mg, 0.407 mmol), and HOBt (52 mg, 0.385 mmol) in DMF (-2 mL) was added t-Butyl N-(3-aminopropyl)carbamate 4 (71 mg, 0.407 mmol) and DIEA (180 &mgr;L, 1.0 mmol). The reaction mixture was stirred 24 h, diluted with EtOAc (150 mL), washed with 1.0 M HCl (2×60 mL), saturated NaHCO3 (2×60 mL), H2O (3×60 mL), dried over MgSO4 and concentrated to give a crude white solid. Purification by silica gel chromatography (25:1 CH2Cl2/MeOH) afforded 194 mg (75% yield) of biphenyl-4,4′-dicarboxylic acid 4′-[(3-(Boc)-amino-propyl)-amide]4-[(2R)-benzyloxy-(1S)-benzyloxycarbamoyl-propyl)-amide] 5 as a white solid. Rf=0.15 (50:1 CH2Cl2/MeOH); LRMS (ES+) m/z 695.2 (C40H46N4O7+H requires 695.35).

[0781] Preparation of Biphenyl-4,4′-dicarboxylic acid 4′-[(3-Boc-amino-propyl)-amide] 4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide] (6). 14 Reagent MW Eq. g/mL mmol Biphenyl diamide (5) 694.82 1.00 0.190 g 0.273 Pd(OH)2 (20%/C) 106.42 0.15 0.020 g 0.040 H2 (g) balloon THF  5.0 mL MeOH  3.0 mL

[0782] A solution of dibenzyl-protected threonine hydroxamic acid 5 (190 mg, 0.273 mrnol) in THF (5 mL) and MeOH (3 mL) was charged with Pd(OH)2 (20%/C, 20 mg, 0.04 mmol) and stirred under a hydrogen atmosphere (balloon pressure) for 16 h. The crude mixture was filtered through a plug of celite eluting with 2:1 MeOH/THF (15 mL) and concentrated to give an orange syrup. Purification by silica gel chromatography (5:1:1 THF/MeOH/CH2Cl2 afforded 110 mg (78% yield) of biphenyl-4,4′-dicarboxylic acid 4′-[(3-Boc-amino-propyl)-amide] 4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide] as a white foam, mp 75-77° C. Rf=0.20 (10:1 CH2Cl2/MeOH); LRMS (ES+) m/z 515.4 (C26H34N4O7+H requires 515.26).

[0783] Preparation of Biphenyl-4,4′-dicarboxylic acid 4′-[(3-amino-propyl)-amide] 4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide] (7). 15 Reagent MW Eq. g/mL mmol Boc-protected 514.57 1.00 0.080 g 0.155 amine (6) TFA  3.0 mL CH2Cl2  3.0 mL

[0784] A flask containing Boc-protected amine 6 (80 mg, 0.155 mmol) was treated with 50% TFA/CH2Cl2 (6.0 mL) and stirred for 2.5 h. The reaction mixture was concentrated by rotary evaporation to give a brown syrup. Purification by RP-HPLC (C18 column, CH3CN gradient 5-70%, 0.1% TFA, UV analysis 300 nm, 36 min) and lyophilization of the collected fractions afforded 14 mg (21% yield) of biphenyl-4,4′-dicarboxylic acid 4′-[(3-amino-propyl)-amide] 4-[((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide] as a white solid. LRMS (ES+) m/z 415.3 (C21H26N4O5 +H requires 415.20); RP-HPLC (300 nm, 36 min run) 18.2 min.

Example 8

[0785] Synthesis of N-(2-(N-hydroxycarbamoyl)(2S)-2-{[4-(4-ethylphenyl)phenyl]carbonylamino}ethyl)acetamide (4) 101

[0786] Preparation of 3-Acetylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (2). 16 102 Reagent MW EQ g/ml mmol Fmoc—DAP—H (1) 326.4 1.0 980 mg 3.0 Acetic anhydride 102.09 1.5 425 uL 4.5 Pyridine 79.1 2.0 483 uL 6.0 THF  20 ml

[0787] Acetic anhydride in THF (5 ml) was added to a cloudy mixture of Fmoc-DAP-H (1) (980 mg, 3.0 mmol) and pyridine (483 uL, 6.0 mmol) in THF (15 ml) with stirring at rt. After 4 hours, the clear pale yellow solution had reacted completely by LCMS. The reaction was evaporated under reduced pressure. The residue was dissolved in EtOAc (150 ml) and washed with 0.1M NaHSO4 (50 ml), water (50 ml), sat. brine (50 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give 1.1 g of crude product as a white solid. The crude product was purified by prep. HPLC to give 0.99 g (90% yield) of acyl-DAP (2).

[0788] Preparation of (2-Acetylamino-1-hydroxycarbamoyl-ethyl)-carbamic acid 9H-fluoren-9-ylmethyl ester trityl resin (3). 17 103 104 Reagent MW EQ g/ml mmol H2N—O—Trt Resin 1.0 120 mg 0.113 Fmoc—DAP(Ac)—H (1) 368.4 5.0 980 mg 0.564 HATU 380 5.0 0.146 g 0.564 DIEA 129.25 10.0 196 ul 1.13 NMP 1.7 ml

[0789] A solution of Fmoc-DAP(Ac)-H (1) (980 mg, 0.56 mmol), HATU (0.146 g, 0.56 mmol) in NMP (1.7 ml) was made. After 2 min. of shaking, the activated acid was added to the deprotected H2N-O-Trt Resin (120 mg, 0.113 mmol) at rt with shaking. [Deprotection of the Fmoc group from the resin was accomplished using 20% piperizine in DMF (4 ml) for 2 hours twice. The resin was drained and washed with DMF (2×5 ml) and DCM (2×5 ml).] After shaking for 20 hours, the reaction was drained and washed with DMF (2×5 ml) and DCM (2×5 ml). The resin was dried and used as is in the next reaction.

[0790] Preparation of N-(2-(N-hydroxycarbamoyl)(2S)-2-{[4-(4-ethylphenyl)phenyl]carbonylamino}ethyl)acetamide (4)

[0791] Preparation of (2-Acetylamino-1-hydroxycarbamoyl-ethyl)-carbamic acid 9H-fluoren-9-ylmethyl ester trityl resin (3). 18 105 106 Reagent MW EQ g/ml mmol Fmoc—DAP(Ac)—Trt Resin (3) 1.0 120 mg 0.113 4′-Etbiphenyl 4-carboxy acid 226.3 5.0  91 mg 0.4 HATU 380 5.0 152 mg 0.4 DIEA 129.25 10.0 140 ul 0.8 NMP 1.0 ml

[0792] The resin was treated with 20% piperizine in DMF (4 ml) for 2 hours twice. The resin was drained and washed with DMF (2×5 ml) and DCM (2×5 ml). The resin was dried in vacuo. A solution of 4′-Ethyl-biphenyl-4-carboxylic acid (9lmg, 0.4 mmol), HATU (152 g, 0.4 mmol) in NMP (1.0 ml) was made. After 2 min. of shaking, the activated acid was added to the deprotected H-DAP(Ac)-Trt resin (120 mg, 0.113 mmol) at rt with shaking. After shaking for 18 hours, the reaction was drained and washed with DMF (2×5 ml) and DCM (2×5 ml). The resin was dried in. vacuo. The product was cleaved from the resin through treatment with a solution of TFA (500 uL), DCM (500 uL) and water (50 uL) for 25 min. The resin was filtered and washed with fresh DCM (2 ml). The combined TFA and DCM fractions are evaporated under reduced pressure. The residue was diluted with CH3CN/water (1:1) (10 ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (1 ml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness. The solid residue was lyophilized again from CH3CN/water (1:1) (5 ml) give 8.6 mg of pure product (4) (˜21% yield).

Example 9

[0793] Synthesis of 4′-Ethyl-biphenyl-4-carboxylic acid (1-hydroxycarbamoyl-2-methanesulfonylamino-ethyl)-amide (3)

[0794] Preparation of 4′-Ethyl-biphenyl-4-carboxylic acid (2-amino-1-hydroxycarbamoyl-ethyl)-amide. trityl resin (2). 19 107 108 Reagent MW EQ g/ml mmol Biphenyl-DAP(Alloc)—Trt Resin (1) 1.0 500 mg 0.35 Dimethyl barbituric acid 156.14 10.0 600 mg 3.5 Pd(PPh3)4 1135.6 1.0 438 mg 0.35 PPh3 262.3 2.0 202 mg 0.7 DCM 11.0 ml

[0795] Pd(Ph3)4 (438 mg, 0.35 mmol) was added to a vial containing biphenyl-DAP(Alloc)-Trt Resin (1) (500 mg, 0.35 mmol), Dimethyl barbituric acid (600 mg, 3.5 mmol) and PPh3 (438 mg, 0.35 mmol) in DCM (11 ml) at rt under argon. The mixture was sparged with argon and shaken for 16 hours. The bright yellow mixture was drained and washed with DMF (8×10 ml) and DCM (8×10). The resin was dried in vacuo to give the deprotected DAP resin 2.

[0796] Preparation of 4′-Ethyl-biphenyl-4-carboxylic acid (1-hydroxycarbamoyl-2-methane sulfonylamino-ethyl)-amide (3). 20 109 110 Reagent MW EQ g/ml mmol Biphenyl-DAP—Trt Resin (2) 1.0 160 mg 0.11 Methanesulfonyl chloride 114.55 10.0  85 uL 1.1 Lutidine 107.16 15.0 190 uL 1.6 DCM 1.5 ml

[0797] Methanesulfonyl chloride (85 uL, 1.1 mmol) was added to a mixture of deprotected DAP resin (2) (160 mg, 0.11 mmol) and lutidine (190 uL, 1.6 mmol) in DCM (1.5 ml). After shaking for 16 hours, the mixture was drained and washed with DMF 10×2 ml) and DCM (5×2 ml). The product was cleaved from the resin through treatment with TFA/water (4:1) (1.5 ml). After shaking for 45 min., the TFA solution was collected from the resin by filtration, and the resin was washed with TFA (1 ml) and TFA/water (1:1) (10 ml). The combined TFA fractions were concentrated under reduced pressure to a reddish-brown solid. The product, identified by LCMS, was purified by prep. HPLC using a 20×50 mm Ultro 120 C18 column running a 22 ml/min 4% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness. The solid residue was lyophilized again from CH3CN/water (1:1) (5 ml) give 4 mg of pure product as a white solid (3) (˜9% yield).

Example 10

[0798] Synthesis of 4′-Ethyl-biphenyl-4-carboxylic acid [2-(3,3-dimethyl-ureido)-1-hydroxycarbamoyl-ethyl]-amide (3) (Continued from compound 2 of Example 9 above) 21 111 112 Reagent MW EQ g/ml mmol Biphenyl-DAP—Trt Resin (2) 1.0 125 mg 0.096 Dimethylcarbamyl chloride 107.5 10.0 103 mg 0.96 Lutidine 107.16 20.0 225 uL 1.92 DCM 1.5 ml

[0799] Dimethylcarbamyl chloride (103 mg, 0.96 mmol) was added to a mixture of deprotected DAP resin (2) (125 mg, 0.096 mmol) and lutidine (225 uL, 1.92 mmol) in DCM (1.5 ml). After shaking at rt for 5 hours, the mixture was drained and washed with DCM (5×2 ml), DMF (5×2 ml) and DCM (5×2 ml). The product was cleaved from the resin through treatment with TFA/water (4:1) (1.5 ml). After shaking for 45 min., the TFA solution was collected from the resin by filtration, and the resin was washed with TFA/water (1:1) (2 ml). The combined TFA fractions were concentrated under reduced pressure to a reddish-brown solid. The product, identified by LCMS, was purified by prep. HPLC using a 20×50 mm Ultro 120 C18 column running a 22 mvmin 4% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness. The solid residue was lyophilized again from CH3CN/water (1:1) (5 ml) give 5 mg of pure product as a white solid (3) (˜13% yield).

Example 11

[0800] Synthesis of 4′-Ethyl-biphenyl-4-carboxylic acid [2-(2-amino-ethylamino)-1-hydroxycarbamoyl-ethyl]-amide (2). 22 113 114 Reagent MW EQ g/ml mmol Biphenyl-DAP-hydroxamate (1) 327.4 1.0  20 mg 0.096 Boc-amino-acetaldehyde 159.19 4.0 6.4 mg 0.4 NaBH3CN 62.84 10.0 3.1 mg 0.05 Acetic acid 60.05 20.0   6 uL 1.00 DCM 1.5 ml

[0801] NaBH3CN (3.1 mg, 0.05 mmol) followed by acetic acid (6 uL, 1.0 mmol) were sequentially added to a stirred suspension of biphenyl-DAP-hydroxamate (1) (20 mg, 0.096 mmol) and Boc-amino-acetaldehyde (6.4 mg, 0.4 mmol) in MeOH (1.5 ml) in a 4 ml vial. The reaction was followed by LCMS. After stirring 12 hours, the cloudy reaction was only 50% complete. The reaction was concentrated under reduced pressure to a thick slurry that was dissolved in DMSO. The product was purified by prep. HPLC using a 20×50 mm Ultro 120 C18 column running a 22 ml/min 3% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness. The dried powder was dissolved in CH3CN/water (1:1) (1 ml) and 1M HCl (700 uL). After heating at 50° C. for 75 min., the reaction mixture was again lyophilized to dryness to produce 7.1 mg of product (2) as a 2xHCl salt white powder (˜17% yield).

Example 12

[0802] Synthesis of N-(1-(N-hydroxycarbamoyl)1S,2R)-2-hydroxypropyl)[4-(2-phenylethynyl)phenyl]carboxamide 115

[0803] Preparation of 4-Phenylethynyl-benzoic acid (3) 23 116 117 Reagent MW EQ g/ml mmol Iodo-benzoate 1 262 1.0 20.0 g 76.34 Ethynyl-benzene 2 102 1.1 8.56 g 83.96 PdCl2(PPh3)2 702 0.012 0.65 g 0.92 CuI 190 0.024 0.35 g 1.83 TEA 101 1.5  16 ml 114.5 d = 0.726 THF (dry & sparged 110 ml with argon for 5 min.)

[0804] The 4-iodo-benzoic acid methyl ester 1 (20.0 g, 76.34 mmol), ethynyl-benzene 2 (8.56 g, 83.96 mmol), PdCl2(PPh3)2 (0.65 g, 0.92 mmol), and CuI (0.35 g, 1.83 mmol) were mixed with THF (110 ml) in a round bottom under argon. The dry THF was sparged with dry, oxygen-free argon for at least 5 min. immediately before use. The reaction was cooled to 10° C. and TEA (16 ml) was added. The cooling bath was removed and the reaction was stirred at RT under argon. After 2.5 h, the reaction was diluted with EtOAc (400 ml) and the solids were filtered off through a pad of celite. The organic filtrate was washed with 1M HCl (60 ml), sat. aq. NaHCO3 (60 ml), water (60 ml), brine (60 ml), dried with Na2SO4, filtered and concentrated under reduced pressure. The crude solid methyl ester was dissolved in MeOH (400 ml), 6M NaOH (30 ml) and water (50 ml). The reaction was stirred at 70° C. until a clear solution was formed (about 1 h). The reaction could be followed by LCMS. The reaction was cooled and diluted with water (500 ml) and hexane (100 ml). The pH was adjusted to pH 6-7. The white solid that formed was collected and washed with water (3×60 ml) and hexane (3×60 ml). The solid 3 was dried in vacuo yielding 17.3 g (approximately quantitative yield in 99% purity).

[0805] Preperation of 3-Hydroxy-2-(4-phenylethynyl-benzoylamino)-butyric acid methyl ester (4) 24 118 119 Reagent MW EQ g/ml mmol 4-Phenylethynyl-benzoic acid (3) 222 1.0 1.55 g 7.0 Threonine methyl ester.HCl 169.65 1.4 1.66 g 9.8 HBTU 380 1.0 2.66 g 7.0 DIEA 125.28 2.5 3.05 ml 17.5 DMF  21 ml

[0806] A solution of threonine (1.66 g, 9.8 mmol) and DIEA (1.53 ml, 8.8 mmol) in DMF (10 ml) was added to a stirred solution of 4-phenylethynyl-benzoic acid 3 (1.55 g, 7.0 mmol) and DIEA (1.53 ml, 8.8 mmol) in DMF (11 ml) at rt. After 12 h, the reaction was diluted with EtOAc (300 ml) and washed with 0.5M HCl (2×60 ml), sat. aq. NaHCO3 (60 ml), 50% diluted brine (60 ml), sat. brine (60 ml), dried with Na2SO4, filtered and concentrated under reduced pressure. Upon drying in vacuo, 2.34 g of white solid was obtained (approximately quantitative yield in 99% purity).

[0807] Preperation of N-(2-Hydroxy-1- hydroxycarbamoyl-propyl)-4-phenylethynyl-benzamide (5) 25 120 121 Reagent MW EQ g/ml mmol Tolanoic-Thr—OMe (4) 340.42 1.0 2.34 g 7.0 H2NOH.HCl 69.49 10.0 4.81 g 70.0 NaOMe 54.02 >11.0 >4.16 g >77.0 MeOH (dry) 50 ml DCM (dry) 30 ml

[0808] A solution of tolanoic-Thr methyl ester (4) (2.34 g, 7.0 mmol) in MeOH (20 ml) and DCM (30 ml) was added to a cooled (−10° C. bath) suspension of hydroxylamine HCl salt (4.81 g, 70.0 mmol) and NaOMe (4.16 g, 77.0 mmol) in MeOH (30 ml). Follow reaction by LCMS. After stirring for 2 hours, the reaction seems to stall at 50% completion. Add an additional 1 equivalent of NaOMe (0.416 g). After 3 hours, the reaction was 75% complete. Add an additional 0.5 equivalent of NaOMe (0.21 g). After 4 hours, the reaction was 90% complete. Add an additional 0.15 equivalent of NaOMe (0.064 g) for a total of 12.65 equivalents of NaOMe. The pH of the reaction was between 11-12 and had reacted about 95% completion. The reaction was diluted with EtOAc (500 ml) and washed with sat. aq. NaHCO3 (2×60 ml), 50% diluted brine (60 ml), sat. brine (60 ml), dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in minimal DMA. The product was purified by prep. HPLC using a reverse phase Ultro 120 C18 column running a 2% gradient (AcCN/water, 0.1% TFA). The purified fractions were lyophilized to dryness. The product as the TFA salt dissolved in AcCN/water (50:50) (80 ml), 1N aq. HCl (13 equivalent) and lyophilized again to give 1.3 g of white powder in 55% yield and >97% purity.

Example 13

[0809] Synthesis of 3-(R)-Amino-2-(S)-(3-phenylethynyl-benzoylamino)-butyl-hydroxamic acid (10)

[0810] Preparation of 3-(R)-Azido-2-(S)-(3-phenylethynyl-benzoylamino)-butyric acid methyl ester (9). 122

[0811] The synthesis of compound 4 is described above. The tolanyl compound (9) was made by the same procedures as for compound (6). The product (9) was obtained in 92% yield (952 mg).

[0812] HPLC(220 nm, 41 min. run) 32.64 min.; HPLC(220 nm, 17 min. run) 15.08 min LCMS: LC(214 nm) 3.16 min., MS(ES+) m/z 363.1 (C20H18N4O3+H requires 363.14).

[0813] Preparation of 3-(R)-Amino-2-(S)-(3-phenylethynyl-benzoylamino)-butyl-hydroxamic acid (10) 26 123 124 Reagent MW Eq. g/ml mmol Amino-Thr-OMe (9) 362.38 1.0 726 mg 2.0 PPh3 262.29 1.0 526 mg 2.0 H2NOH.HCl 69.49 10.0 1.4 g 20.0 NaOMe 54.02 ˜12.0 1.3 g 24.0 THF (dry) 20 ml MeOH (dry) 20 ml

[0814] Triphenylphosphine (526 mg, 2.0 mmol) was added to a stirred solution of tolanyl-azido-Thr methyl ester (9) (726 mg, 2.0 mmol) at rt. After 3 days the reaction reached completion as judged by TLC (EtOAc/Hex (2:1)) and LCMS. The reaction was concentrated under reduced pressure to give an ivory colored solid. The crude amino-phosphine was dissolved in MeOH (20 ml) to give a pale yellow solution. To the solution of amino-phosphine was added sequentially hydroxylamine HCl salt (1.4 g, 20.0 mmol) followed by fresh solid NaOMe powder (1.3 g, 24.0 mmol) to make a milky pH 10 suspension. After 36 h, the reaction was complete by LCMS. The reaction was evaporated under reduced pressure to give a yellow solid that was dried in vacuo. The crude product (2.75 g) was triturated with ether (3×50 ml) to remove impurities (P(O)Ph3) and then was dissolved in abs. EtOH (120 ml) with sonication for 15 min. A fine white powder was suction filtered off, and the clear yellow ethanolic portion was concentrated to a small volume. The crude product was dissolved in DMSO (8 ml) and purified by preparative HPLC (Ultro 120 C18 75×300 mm column) running a gradient (AcCN/water, 0.1% TFA) from 5 to 70% for 55 min. The purified fractions were pooled together and lyophilized to dryness. The product as the TFA salt was dissolved in AcCN/water (50:50) (100 ml), 1N aq. HCl (1 equivalent) and lyophilized again to give 325 mg of light yellow powder as the HCl salt (43% yield).

[0815] HPLC(220 nm, 41 min.run) 18.31 min.; HPLC(220 nm, 17 min.run) 9.11 min; LCMS: LC(214 nm) 1.91 min., MS(ES+)m/z 338.1 (Cl19H19N3O3+H requires 338.14).

Synthesis of 4′-(N-Acylamnino)-Tolan Dap Analogs

Example 14

[0816] Synthesis of 4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide 125

[0817] Preparation of 2-N-Boc-amino-N-(4-iodo-phenyl)-acetamide (2). 27 126 127 Reagent MW Eq. g/mL mmol Boc-Gly-OH 175.19 1.00 1.752 g 10.0 4-Iodoaniline (1) 219.03 1.04 2.290 g 10.4 EDCI 191.71 1.04 1.994 g 10.4 HOBt 135.13 1.00 1.351 g 10.0 DCM 18 mL DMF 1 mL

[0818] A solution of Boc-Gly-OH (1.752 g, 10.0 mmol) in DCM (18 mL) and DMF (1 mL) was treated with EDCI (1.994 g, 10.4 mmol) and HOBt (1.351 g, 10.0 mmol). After stirring 15 min, 4-iodoaniline 1 (2.290 g, 10.4 mmol) was added and the reaction monitored by TLC (25:1 DCM/MeOH (Rf=0.6)). After 24 h the solution was diluted with EtOAc (250 mL), washed with 1.0 M HCl (3×100 mL), sat. NaHCO3 (3×100 mL), brine (3×100 mL), dried over MgSO4, filtered and concentrated in vacuo to afford 2.900 g (77% yield) of a white solid.

[0819] Preparation of (2S)-3-N-Boc-amino-(4-ethynyl-benzoylamino)-propionic acid methyl ester (4). 28 128 129 Reagent MW Eq. g/mL mmol 4-Ethynylbenzoic acid (3) 146.14 1.0 0.910 g 6.22 H-Dap(Boc)—OMe—HCl 254.71 1.2 1.903 g 7.47 EDCI 191.71 1.2 1.432 g 7.47 HOBt 135.13 1.1 0.910 g 6.73 DIEA 129.25 3.2 3.5 mL 20.0 DMF 50 mL

[0820] Triethylamine (3.5 mL, 20.0 mmol) was added to a stirred solution of 4-ethynylbenzoic acid 3 (910 mg, 6.22 mmol), H-Dap(Boc)-OMe hydrochloride (1.903 g, 7.47 nmnol), EDCI (1.432 g, 7.47 mmol), and HOBt (910 mg, 6.73 mmol) in DMF (50.0 mL). After stirring 20 h, the reaction mixture was diluted with EtOAc (400 mL), washed with 1.0 M HCl (2×100 mL), saturated NaHCO3 (2×100 mL), H2O (4×100 mL), dried over MgSO4, filtered and concentrated in vacuo to give 2.140 g (99% yield) of a tan solid, mp=110-111° C. LRMS (ES+) m/z 346.9 (Cl8H22N2O5 +H requires 347.10). 130

[0821] To a suspension of methyl (2S)-3-[(tert-butoxy)carbonylamino]-2-[(4-ethynylphenyl)carbonylamino]propanoate (4) (200 mg, 0.577 mmol) and 2-[(tert-butoxy)carbonylamino]-N-(4-iodophenyl)acetamide (2) (476 mg, 1.26 mmol) was added Et3N (350 &mgr;L, 2.5 mmol). The solution was purged with a stream of N2 for several minutes and PdCl2(PPh3)2 (20 mg, 0.028 mmol) and CuI (10.6 mg, 0.055 mmol) were added. The reaction mixture was stirred at ambient temperature for 22 h and then concentrated by rotary evaporation. The crude black residue was chromatographed twice by silica gel chromatography (30:1 CH2Cl2/MeOH) to give 285 mg (83%) of methyl (2S)-3-[(tert-butoxy)carbonylamino]-2-({4-[2-(4-{2-[(tert-butoxy)carbonylamino]acetylamino}phenyl)ethynyl]phenyl}carbonylamino) propanoate (5) as a yellow foam. 131

[0822] To a solution of hydroxylamine hydrochloride (98 mg, 1.41 nimol) in MeOH (1.3 mL) at 0° C was added 25 wt % NaOMe (460 mg, 2.13 mmol). The solution was stirred at 0° C. for 15 min and then charged with a solution of methyl (2S)-3-[(tert-butoxy)carbonylamino]-2-({4-[2-(4-{2-[(tert-butoxy)carbonylamino]acetylamino}phenyl)ethynyl]phenyl}carbonylamino) propanoate (4) (279 mg, 0.469 mmol) in THF (1.5 mL) and MeOH (0.6 mL). The reaction was stirred at 0° C. for 30 min and at room temperature for 2.5 h. The reaction mixture was diluted with 4:1 CHCl3/iPrOH (50 ml) and washed with 0.1 M HCl (30 mL). The layers were separated and the aqueous layer extracted once more with 4:1 CHCl3/iPrOH (30 ml). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The crude residue was suspended in 10:1 CH2Cl2/MeOH (4 mL), filtered, and washed with 50:1 CH2Cl2/MeOH (2 mL) and Et2O (10 mL) to afford 180 mg (64%) of N-(4-{2-[4-(N-{1-(N-hydroxycarbamoyl)(1S)-2-[(tert-butoxy)carbonylamino]ethyl}carbamoyl)phenyl]ethynyl}phenyl)-2-[(tert-butoxy)carbonylamino]acetamide (6) as a white powder.

[0823] To an oven-dried flask containing N-(4-{2-[4-(N-{1-(N-hydroxycarbamoyl)(1S)-2-[(tert-butoxy)carbonylamino]ethyl}carbamoyl)phenyl]ethynyl}phenyl)-2-[(tert-butoxy)carbonylamino]acetamide (6) (130 mg, 0.218 mmol) was added 1:1 TFA/CH2Cl2 (2.5 mL). The resulting pink solution was stirred for 2 h and concentrated to give a pink gum. The crude residue was rinsed with CH2Cl2 (4 mL), concentrated by rotary evaporation and dissolved in THF (2 mL) and MeOH (0.4 mL). A solution of 4 M HCl in dioxane (200 &mgr;L) was added and the resulting precipitate filtered and washed with Et2O (10 mL) to afford 90 mg of 4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]benzamide as a pale tan powder.

Reaction of Iodoaniline with Bromoacetyl Bromide

[0824] 132

[0825] Bromoacetyl bromide (175 &mgr;L, 2.00 mmol) was added dropwise over 5 minutes to a solution of 4-iodoaniline (438 mg, 2.00 mmol) and Et3N (280 &mgr;L, 2.00 mmol) in benzene (5 mL). The reaction was stirred 1 hour, treated with morpholine (1.0 mL, 11.5 mmol) and stirred overnight. The reaction mixture was diluted with EtOAc (200 mL), washed with aqueous 0.1 M KOH (50 nmL), H2O (50 mL), dried over MgSO4 and concentrated to give a yellow oil. Purification by silica gel chromatography (100:1 CH2Cl2/MeOH) afforded 630 mg (91%) of N-(4-iodophenyl)-2-morpholin4-ylacetamide as a waxy tan solid. This product was converted to analogues in a similar manner as Example 14.

Example A

[0826] Preparation of 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester. 29 133 134 135 Reagent MW EQ g/ml mmol H—DAP(Boc)—OMe (1) 254 1.05 5.93 g 23.3 4-Iodo-benzoic acid 248 1.0 5.49 g 22.2 HOAT 136.1 1.02 3.08 g 22.6 EDC 191.71 1.02 4.33 g 22.6 DIEA 129.25 2.5 9.7 ml 55.1 DMF 85 ml

[0827] DIEA (9.7 ml, 55.1 mmol) was added to a stirred solution of 4-iodo-benzoic acid (5.49 g, 22.2 mmol), HOAT (3.08 g, 22.6 mmol), EDC (4.33 g, 22.6 mmol) in DMF (85 ml). After 2 min., the H-DAP(Boc)-OMe (1) was added in one portion. After 12 hours, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (1:1) (500 ml). The organic phase-was washed with 1N HCl (2×80 ml), IN NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (1:1). The fractions with product were evaporated to give 9.3 g of product (3-tert-Butoxycarbonylamino-2-(4-iodo-benzoylamino)-propionic acid methyl ester) in 93% yield. This product was converted to analogues in a similar manner as the aforementioned Examples.

Example 15

[0828] N-(1-(N-hydroxycarbamoyl)(1S,2R)-2-hydroxypropyl)(4-{2-[4-(morpholin4-ylmethyl)phenyl]ethynyl}phenyl)carboxamide (5) 136

Preparation of (2S, 3R)-2-[4-(4-formyl-phenylethynyl)-benzoylaminol-3-hydroxy-butyric acid methyl ester (3).

[0829] 30 137 138 Reagent MW Eq. g/ml mmol Ethynylbenzene (1) 261.27 1.0 0.745 g 2.85 4-Iodobenzaldehyde (2) 232.00 1.4 0.902 g 3.89 PdCl2(PPh3)2 701.89 0.03 0.070 g 0.10 CuI 190.44 0.06 0.034 g 0.18 Et3N 101.19 2.3 0.90 mL 6.5 THF 50 mL

[0830] A solution of alkyne 1 (745 mg, 2.85 mmol), 4-iodobenzaldehyde 2 (902 mg, 3.89 mmol), and Et3N (900 &mgr;L, 6.5 mmol) in THF (50 mL) was purged with a stream of N2 for two minutes and then treated with PdCl2(PPh3)2 (70 mg, 0.10 mmol) and CuI (34 mg, 0.18 mmol). The reaction mixture was stirred 40 h, concentrated by rotary evaporation and purified by silica gel chromatography (40:1 DCM/MeOH) to give 0.833 g (80% yield) of (2S, 3R)-2-[4-(4-formyl-phenylethynyl)-benzoylamino]-3-hydroxy-butyric acid methyl ester 3 as a pale yellow powder, mp=143-144° C. Rf=0.3 (25:1 DCM/MeOH); LRMS (ES+) m/z 366.1 (C21H19NO5 +H requires 366.13); HPLC (300 nm, 47 min) 15.3 min.

Preparation of (2S, 3R)-3-Hydroxy-2-[4-(4-morpholin4-ylmethyl-phenylethynyl)-benzoylamino]-butyric acid methyl ester (4).

[0831] 31 139 140 Reagent MW Eq. g/ml mmol Tolanylaldehyde (3) 365.38 1.0 0.822 g 2.25 Morpholine 87.12 1.3 0.260 mL 2.97 NaBH(OAc)3 211.94 1.4 0.670 g 3.16 THF 15 ml

[0832] Sodium triacetoxyborohydride (0.670 g, 3.16 mmol) was added to a solution of benzaldehyde 3 (0.822 g, 2.25 mmol) and morpholine (260 &mgr;L, 2.97 mmol) in THF (15 mL) under N2 atmosphere and the reaction monitored by TLC (25:1 DCM/MeOH, Rf=0.2). After stirring 4 h, the reaction mixture was quenched with saturated NaHCO3 (150 mL), extracted with EtOAc (3×100 mL), dried over MgSO4, filtered and concentrated to give a yellow syrup. Purification by silica gel chromatography (35:1 DCM/MeOH) afforded 0.844 g (86% yield) of 4 as a sticky white foam.

Preparation of (2S, 3R)-N-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-(4-morpholin-4-ylmethyl-phenylethynyl)-benzamide (5).

[0833] 32 141 142 Reagent MW Eq. g/ml mmol Methyl ester (4) 436.50 1.0 0.829 g 1.90 NH2OH—HCl 69.49 3.0 0.400 g 5.76 NaOMe (25 wt%) 54.02 4.5 1.860 g 8.60 MeOH 8 mL THF 3 mL

[0834] Sodium methoxide (25 wt % in MeOH, 1.860 g, 8.60 mmol) was added to a stirred solution of hydroxylamine hydrochloride (400 mg, 5.76 mmol) in anhydrous MeOH (5 mL) at 0° C. under N2 atmosphere. After stirring 20 min, a solution of methyl ester 4 (829 mg, 1.90 mmol) in 1:1 MeOH/THF (6 mL) was added and the reaction mixture stirred at 0° C. for 1 h and at room temperature for 4 h. The reaction was quenched with 1.0 M HCl (6 mL), concentrated by rotary evaporation to remove organic solvents, and diluted with DMSO (4 mL). Analytical RP-HPLC (C18 column, CH3CN gradient 5-35%, 0.1% TFA, UV analysis 300 nm, 16 min) indicated a purity of 85% for the crude product mixture. Purification by preparative RP-HPLC and lyophilization of the collected fractions gave 701 mg (81%) of 5 as a fluffy white solid. LRMS (ES+) m/z 438.1 (C24H27N3O5+H requires 438.20); RP-HPLC (300 nm, 16 min run) 8.7 min.

Resin Procedures for Synthesizing Tolanyl hydroxamates

Example 16

[0835] Synthesis of 4-[(4-{[(benzylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino)carbonylipropyl}benzamide 143

[0836] 1. Coupling to Fmoc Hydroxylamine Resin

[0837] The resin was pre-swelled by adding DCM and shaking for 30 min. The resin was drained, 20% piperdine was added in DMF, the resin was shaken 1.25 hours, and finally drained and washed in 2×DMF and 2×DCM. After draining comnpletely, 20% piperdine in DMF was added to attain cleavage in 1.25 hours. The resin was washed 4×DMF, 4×DCM and drained completely. In a separate flask, the amino acid (Fmoc-Thr tBu-OH, or Fmoc-DAP Boc-OH, 4 eq) was mixed, HATU (4 eq), DMF (60 ml) and Hunig's (8 eq) base were added and stirred for 2-3 min. The mixture was added to the resin and shaken 20-24 hours. Subsequently, the resin was drained and run with a standard wash (1×DCM, 4×DMF and 4×DCM). The Fmoc was removed from the amino acid by adding 20% piperdine in DMF and shaken 1.25 hours, drained, and given the standard wash (1×DCM, 4×DMF and 4×DCM).

[0838] 2. Coupling of 4-iodobenzoic Acid to Amino Acid Resin

[0839] A mixture of 4-iodobenzoic acid (4 eq), HBTU (4 eq), DMF (60 ml) was shaken for several minutes. Hunig's base (8 eq) was subsequently added and the mixture was shaken further for 2-3 min. The pre-activated mixture was then added to the prepared Thr or DAP resin (Fmoc removed, 7.5 g, 5.775 mmol). The reaction is shaken 12-16 hours followed by the standard wash (1×DCM, 4×DMF and 4×DCM).

[0840] 3. Alkyne Coupling on Resin

[0841] To the 4-iodobenzoic resin (4 g, 3.08 mmol) was added 4-aminophenylacetylene (3 eq), Pd(PPh3)2Cl2 (0.04 eq), CuI (0.08 eq) and THF (purged with Argon). After mixing for 1 min., TEA (4.5 eq) was added and the reaction was shaken 12 hours at RT under argon.

[0842] 4. Aniline Coupling with Bromoacetyl Chloride on Resin

[0843] To aniline resin (4 g, 3.08 mmol) was added DCM (30 ml) lutidine (10 eq) and shaken for 1 min. Bromoacetyl chloride (8 eq) in DCM (5 ml) was added slowly. After the addition, the slurry was shaken for 1.5 to 1.75 hours. Subsequent draining and a wash with 2×DCM, 4×DMF and 4×DCM was then performed.

[0844] 5. Displacement with Amines on Resin

[0845] To the bromoacetyl resin (125 mg), was added NMP (1.5 ml) followed by amine (0.2 g or ml, ie excess) and the slurry was shaken for 12-16 hours at RT. To neutralize the salt, TEA was added. The imidazole was heated at 38° C. for 24 h (in the case of anilines, they were heated at 38° C. for 48 h). The reaction mixture was drained and washed 4×DMF and 4×DCM.

[0846] 6. Cleavage from Resin and Deprotection of Thr tBu and DAP Boc

[0847] The resin (125 mg) was soaked in TFA/water (80:20 v/v) (1.5 ml) at RT for 45 min. Upon cleavage the solution was collected and the resin was washed with more TFA/water mixture (0.75 ml). To the TFA/product solution was added acetonitrile/water solution (1:1 v/v, 10 ml) and pure water (2.5 ml). The-mixture was frozen in liquid nitrogen for 18 15 min and lyophilized. The dry residue was dissolved in the acetonitrile/water solution (1:1 v/v, 10 ml) again followed by addition of 1M aq. HCl (1.2 eq per basic nitrogen), frozen, and lyophilized to a powder.

Synthesis of 3′-Nitro-Tolan Threonine Hydroxamic Acid

Example 17

[0848] (1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-(3-nitro-phenylethynyl)-benzamide 144

Preparation of (1S,2R)-N-(2-tert-butoxy-1-hydroxycarbamoyl-propyl)-4-ethynyl-benzamide on Hydroxylamine 2-chlorotrityl Resin (3).

[0849] 33 Reagent MW Eq. g/mL mmol Fmoc-threonine/resin (1) 0.70 mmol/g 1.0 0.522 g 0.365 4-Ethynylbenzoic acid (2) 146.14 3.0 0.160 g 1.10 DIC 126.20 4.9  0.28 mL 1.79 HOBt 135.13 3.0 0.148 g 1.10 DIEA 129.25 6.3  0.40 mL 2.30 DCM  1.0 mL DMF  3.0 mL

[0850] The resin 1 (0.522 g, 0.365 mmol, 0.70 mmol) was swelled in DCM (5 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (6 mL) for 1 hour, washed with DMF (4×6 mL) and DCM (4×6 mL) and drained completely. In a separate flask, 4-ethynylbenzoic acid 2 (0.160 g, 1.10 mmol), DIC (0.280 mL, 1.79 mmol), HOBt (0.148 g, 1.10 mmol) and DIEA (0.4 mL, 2.30 mmol) were dissolved in DCM (1 mL) and DMF (4 mL), stirred 15 min and added to the resin. After shaking for 36 h, the mixture was drained, washed with DMF (4×6 mL) and DCM (4×6 mL) and dried in vacuo to give 0.495 g of a yellow resin.

Preparation of (1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-(3-nitro-phenylethynyl)-benzamide (5).

[0851] 34 Reagent MW Eq. g/mL mmol Alkyne on resin (3) 0.70 mmol/g 1.0  100 mg 0.070 1-Iodo-3-nitrobenzene (4) 249.01 5.0 87.1 mg 0.350 PdCl2(PPh3)2 701.89 0.2 10.0 mg 0.014 CuI 190.44 0.5  7.0 mg 0.036 Et3N 101.19 15  150 &mgr;L 1.10 DMF  1.5 mL

[0852] Resin 3 (100 mg, 0.070 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 1-iodo-3-nitrobenzene 4 (87.1 mg, 0.350 mmol) and Et3N (150 &mgr;L, 1.10 mmol) in DMF (1.5 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2(PPh3)2 (10.0 mg, 0.014 mmol) and CuI (7.0 mg, 0.036 mmol) were added and the mixture shaken for 26 h. The resin was drained, washed with DMF (3×2 mL), DCM (3×2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractions afforded 6.0 mg (22% yield) of (1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-(3-nitro-phenylethynyl)-benzamide as a white foam. LRMS (ES+) m/z 384.2 (C19H17N3O6+H requires 384.15); RP-HPLC (300 nm, 28 min run) 15.2 min.

Synthesis of 4′-Trifluoromethoxy-Tolan Dap Hydroxamic Acid

Example 18

[0853] (1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy-phenylethynyl)-benzamide (5) 145

[0854] Preparation of (1S)-N-(2-(Boc)-amino-1-hydroxycarbamoyl-ethyl)-4-ethynyl-benz-amide on Hydroxylamine 2-chlorotrityl Resin (3). 35 Reagent MW Eq. g/mL mmol Fmoc-Dap/resin (1) 0.70 mmol/g 1.0 1.330 g 0.931 4-Ethynylbenzoic acid (2) 146.14 3.0 0.408 g 2.793 DIC 126.20 4.8  0.70 mL 4.470 HOBt 135.13 3.0 0.377 g 2.793 DIEA 129.25 6.2  1.0 mL 5.7 DCM  10.0 mL DMF  2.0 mL

[0855] The resin 1 (1.330 g, 0.931 mmol, 0.70 mmol/g) was swelled in DCM (15 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (20 mL) for 1 hour, washed with DMF (3×15 mL) and DCM (3×15 mL) and drained completely. In a separate flask, 4-ethynylbenzoic acid 2 (0.408 g, 2.793 mmol), DIC (0.70 mL, 4.470 mmol), HOBt (0.377 g, 2.793 mmol) and DIEA (1.0 mL, 5.7 mmol) were dissolved in DCM (10 mL) and DMF (2 mL), stirred 15 min and added to the resin. After shaking for 36 h, the mixture was drained, washed with DMF (3×15 mL) and DCM (3×15 mL) and dried in vacuo to give 1.290 g of a yellow resin.

[0856] Preparation of (1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy-phenylethynyl)-benzamide (5). 36 Reagent MW Eq. g/mL mmol Alkyne on resin (3) 0.70 mmol/g 1.0  120 mg 0.084 4-CF3O-iodobenzene (4) 287.99 4.0 96.8 mg 0.336 PdCl2(PPh3)2 701.89 0.3 18.0 mg 0.025 CuI 190.44 0.5  8.0 mg 0.042 Et3N 101.19 13  150 &mgr;L 1.10 DMF  2.0 mL

[0857] Resin 3 (120 mg, 0.084 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-(trifluoromethoxy)iodobenzene 4 (96.8 mg, 0.336 mmol) and Et3N (150 &mgr;L, 1.10 mmol) in DMF (2.0 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2(PPh3)2 (18.0 mg, 0.025 mmol) and CuI (8.0 mg, 0.042 mmol) were added and the mixture shaken for 24 h. The resin was drained, washed with DMF (3×2 mL), DCM (3×2 mL) and cleaved with 10% TFA/DCM (2.0 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-55%, 0.1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractions afforded 9.0 mg (25% yield) of (1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy-phenylethynyl)-benzamide as a white solid. LRMS (ES+) m/z 408.0 (C19H16F3N3O4+H requires 408.11); RP-HPLC (300 nm, 28 min run) 18.0 min.

Example 19

[0858] Synthesis of N-(1-(N-hydroxycarbamoyl)(1S,2R)-2-hydroxypropyl)[4-(4-phenylbuta-1,3-diynyl)phenyl]carboxamide 37 146 147 148 149 150 151 Reagent MW EQ g/ml mmol Dibromovinylbenzoic acid (2) 320 1.0 5.76 g 18.0 Ethynyl-benzene 102 1.4 2.57 g 25.2 Pd2dba3 915 0.01 164 mg  0.18 (1% cat.) TMPP 352 0.04 253 mg  0.72 (4%) TEA 101 3.0 7.5 ml 54.0 DMF 60 ml degassed with argon

[0859] The 4-(2,2-Dibromo-vinyl)-benzoic acid methyl ester (2) was made by the method of Wang Shen and Le Wang in J.Org.Chem. 1999, 64, 8873-8879.

[0860] A solution of 4-(2,2-dibromo-vinyl)-benzoic acid methyl ester (2) (5.76 g, 18.0 mmol), ethynyl-benzene (2.57 g, 25.2 mmol), Pd2dba3 (164 mg, 0.18 mmol), tris(4-methoxyphenyl) phosphine (TMPP) (253 mg, 0.72 mmol) were dissolved in argon sparged (5 min.) DMF (60 ml). The reaction was sparged with argon for 1 min. TEA (7.5 ml, 54.0 mmol) was added to the stirred reaction mixture that was then heated under argon at 85° C. for 3.5 hours. The reaction was found complete by LCMS. The reaction was cooled to rt and diluted with EtOAc/hexane (1:1) (300 ml). The organic phase was washed with 1M HCl (2×50 ml), 1M NaOH (3×50 ml), water (2×50 ml), sat. brine (50 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to obtain 5.25 g of crude product as an oil. The oil was treated with approximately 20 ml of a solution of 20% EtOAc/hexane that was heated to dissolve the residue. The walls of the flask were washed with the 20% EtOAc/hexane solution (5 ml) that upon cooling gave 1.45 g of pure product (31% yield) as a white solid. The balence of the crude reaction product was purified by flash chromatography using EtOAc (8%)/hexane as eluant. The pure fractions were evaporated and dried in vacuo to give addition product typically 25-30% addition yield.

[0861] 4-(4-Phenyl-buta-1,3-diynyl)-benzoic acid methyl ester (4) was made according to the method of Wang Shen and Sheela A. Thomas in Org.Lett. 2000, 2(18), 2857-2860.

Preparation of 4-(4-Phenyl-buta-1,3-diynyl)-benzoic acid (5)

[0862] A 3M aq. solution of NaOH (20 ml) was added to a stirred solution of methyl ester 4 (1.45 g, 5.6 mmol) in MeOH (100 ml) at rt. The reaction solution was heated to reflux for 45 min. until the reaction turned clear. All of the starting material was gone by TLC and HPLC. The reaction was cooled to rt and some MEOH (˜50 ml) was removed by evaporation under reduced pressure. Water (100 ml) was added to the mixture. Conc. HCl was added dropwise to the stirred solution until acidic by pH paper (pH2). The white precipitate that formed was collected by suction filtration. The solid was washed with water (3×20 ml) and hexane (2×20 ml) to give after drying 1.35 g of product acid 5 in 99% yield.

[0863] Subsequent conversion of compound 5 to compound 7 was performed according to the method described in Example 12 for the synthesis of N-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-phenylethynyl-benzamide (compound 5). LCMS MH+363.13.

Example B

[0864] Synthesis of N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2-oxoethyl]-4-[4-(4-aminophenyl)buta-1,3-diynyl]benzamide

[0865] Preparation of 2-{4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonylamino-propionic acid methyl ester (2). 38 152 153 Reagent MW EQ g/ml mmol H-DAP(Boc)—OMe 254 1.05 5.12 g 20.1 1,3-diynyl benzoic acid (1) 261.3 1.0 5.0 g 19.1 HOBT 135.1 1.05 2.72 g 20.1 EDC 191.71 1.05 3.85 g 20.1 DIEA 129.25 3.0. 10.5 ml 60.3 DMF 80 ml

[0866] DIEA (10.5 ml, 60.3 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (1) (5.0 g, 19.1 mmol), HOBT (2.72 g, 20.1 mmol), EDC (3.85 g, 20.1 mmol) in DMF (80 ml). After 2 min., the H-DAP(Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4:1) (500 ml). The organic phase was washed with 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexajie (4:1). The fractions with product were evaporated to give 8.02 g of product in 91% yield. Subsequent conversion of compound 2 to the final hydroxamic acid (for example, Example 892)was performed according to the method described in Example 12 for the synthesis of N-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-phenylethynyl-benzamide (compound 5).

Synthesis of 4-(Buta-1,3-diynyl)-benzoic Acid (4) for making 1,3-diynyl analogues (such as Example 20 below)

[0867] 154

Preparation of 4-(4-trimethylsilanyl-buta-1,3-diynyl)-benzoic acid methyl ester (3).

[0868] 39 155 156 Reagent MW Eq. g/ml mmol Methyl 4-iodobenzoate (2) 262.04 1.0 4.510 g 17.2 Trimethylsilylbutadiyne (1) 122.24 2.5 5.240 g 42.8 PdCl2(PPh3)2 701.89 0.04 0.483 g 0.690 CuI 190.44 0.08 0.262 g 1.37 Et3N 101.19 3.0 7.2 mL 52.0 CH3CN 50 mL

[0869] A solution of methyl 4-iodobenzoate 2 (4.510 g, 17.2 mmol), PdCl2(PPh3)2 (483 mg, 0.690 mmol), and CuI (262 mg, 1.37 mmol) in CH3CN (50 mL) was cooled to 0° C. under N2 atmosphere in the absence of light. Triethylamine (7.2 mL, 52.0 mmol) was added, followed by trimethylsilyl-1,3-butadiyne 1 (5.240 g, 42.8 mmol) and the reaction stirred 3 h at 0° C. and 30 h at ambient temperature. Removal of solvent by rotary evaporation afforded a crude black residue that was purified by silica gel chromatography (95:5 hexanes/EtOAc) to give 3.450 g (79% yield) of 4-(4-trimethylsilanyl-buta-1,3-diynyl)-benzoic acid methyl ester 3 as a brown solid, mp=67-68° C.

Preparation of 4-(buta-1,3-diynyl)-benzoic acid (4).

[0870] 40 157 158 Reagent MW Eq. g/ml mmol Methyl ester (3) 252.34 1.0 3.420 g 13.5 KOH 56.11 4.9 3.700 g 65.9 H2O 10 mL THF 26 mL

[0871] Potassium hydroxide (3.700 g, 65.9 mmol) was dissolved in H2O (10 mL) and added to a solution of 4-(4-trimethylsilanyl-buta-1,3-diynyl)-benzoic acid methyl ester 3 (3.420 g, 13.5 mmol) in THF (26 mL) in the absence of light. After stirring 16 h, the reaction was quenched with 1.0 M HCl (120 mL) and the resulting precipitate was filtered, washed with 1:1 hexanes/benzene (150 mL) and dried in vacuo to afford 2.100 g (91% yield, 98% pure) of 4-(buta-1,3-diynyl)-benzoic acid 4 as a brown solid, mp>230° C. Although diyne 4 was found to be unstable at room temperature it could be stored for several weeks at 0° C. with only small amounts of decomposition observed by TLC. Rf=0.2 (4:1 Hexanes/EtOAc); HPLC (300 nm, 28 min run) 16.0 min; LRMS (ES+) m/z 171.0 (C11H6O2+H requires 171.04).

Synthesis of a 3′-Nitrophenyl-Diacetylenic-Dap Hydroxamic Acid

Example 20

[0872] N-(1-(N-hydroxycarbamoyl)(1S)-2-aminoethyl){4-[4-(3-nitrophenyl)buta-1,3-diynyl]phenyl}carboxamide (6) 159

Preparation of Fmoc-Dap(Boc)-NHOH on hydroxylamine 2-chlorotrityl resin (2).

[0873] 41 160 Reagent MW Eq. g/mL mmol Hydroxylamine resin (1) 0.77 mmol/g 1.0 3.288 g 2.53 Fmoc-Dap(Boc)-OH 426.47 3.0 3.175 g 7.44 HATU 380.25 3.0 2.829 g 7.44 DIEA 129.25 10.0 4.3 mL 24.7 DMF 35 mL

[0874] A suspension of N-Fmoc-hydroxylamine 2-chlorotrityl resin (3.288 g, 2.53 mmol, 0.77 mmol/g, Novabiochem) in DCM (40 mL) was shaken for 2 h and drained. The resin was treated with 20% piperidine in DMF (40 mL) for 1 hour, washed with DMF (2×40 mL), treated a second time with 20% piperidine in DMF (40 mL), washed with DMF (3×40 mL) and DCM (3×40 mL) and drained completely. In a separate flask, Fmoc-Dap(Boc)-OH (3.175 g, 7.44 mmol), HATU (2.829 g, 7.44 mmol) and DIEA (4.3 mL, 24.7 mmol) were dissolved in DMF (35 mL), stirred three minutes and added to the resin. After shaking for 48 h, the mixture was drained, washed with DMF (4×40 mL) and DCM (4×40 mL) and dried in vacuo to give 3.530 g of a yellow resin.

Preparation of (S)-N-(2-N-Fmoc-amino-1-hydroxycarbamoyl-ethyl)-4-buta-1,3-diynyl-benzamide on hydroxylamine 2-chlorotrityl resin (4).

[0875] 42 161 162 Reagent MW Eq. g/mL mmol Fmoc-Dap(Boc)/resin (2) 0.71 mmol/g 1.0 3.530 g 2.53 Butadiynyl benzoic acid (3) 170.16 2.5 1.076 g 6.32 EDCI 191.71 3.0 1.457 g 7.60 HOBt 135.13 3.0 1.048 g 7.75 DIEA 129.25 5.0 2.2 mL 12.6 DCM 25 mL DMF 5 mL

[0876] The resin 2 (3.530 g, 2.53 mmol, 0.71 mmol/g) was swelled in DCM (40 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (40 mL) for 1 hour, washed with DMF (4×40 mL) and DCM (4×40 mL) and drained completely. In a separate flask, 4-buta-1,3-diynyl-benzoic acid 3 (1.076 g, 6.32 mmol), EDCI (1.457 g, 7.60 mmol), HOBt (1.048 g, 7.75 mmol) and DIEA (2.2 mL, 12.6 mmol) were dissolved in DCM (25 mL) and DMF (5 mL), stirred 45 min and added to the resin. After shaking for 48 h, the mixture was drained, washed with DMF (4×40 mL) and DCM (4×40 mL) and dried in vacuo to give 3.35 g of a pale brown resin.

Preparation of (S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-[4-(3-nitro-phenyl)-buta-1,3-diynyl]-benzamide (6).

[0877] 43 163 164 Reagent MW Eq. g/mL mmol Diacetylene on resin (4) 0.77 mmol/g 1.0 176 mg 0.135 1-Iodo-3-nitrobenzene (5) 249.01 3.5 118 mg 0.474 PdCl2(PPh3)2 701.89 0.07 6.0 mg 0.009 CuI 190.44 0.38 10.0 mg 0.052 Et3N 101.19 10.6 200 &mgr;L 1.43 DMF 3.0 mL

[0878] Resin 4 (176 mg, 0.135 mmol) was swelled in DCM (3 mL) for 1 h and drained. A solution of 1-iodo-3-nitrobenzene 5 (118 mg, 0.474 mmol) and Et3N (200 &mgr;L, 1.43 mmol) in DMF (3.0 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2(PPh3)2 (6.0 mg, 0.009 mmol) and CuI (10.0 mg, 0.052 mmol) were added and the mixture shaken for 36 h. The resin was drained, washed with DMF (4×3 mL), DCM (4×3 mL) and cleaved with 10% TFA/DCM (2 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (2 mL). The cleavage fractions were combined, treated with neat TFA (4.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 30 min) and lyophilization of the collected fractions afforded 12.0 mg (22%) of 470 as a white solid. LRMS (ES+) m/z 392.9 (C20H16N4O5+H requires 393.11); RP-HPLC (300 nm, 30 min run) 14.9 min.

Synthesis of 4′-Benzamide Diacetylene Dap Hydroxamic Acid

Example 21

[0879] N-((2S)-amino-1-hydroxycarbamoyl-ethyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide (3) 165

Preparation of N-((2S)-amino-1-hydroxycarbamoyl-ethyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide (3)

[0880] 44 Reagent MW Eq. g/mL mmol Alkyne on resin (1) 0.77 mmol/g 1.0  145 mg 0.111 4-Ethynylbenzamide (2) 430.54 2.6  124 mg 0.288 PdCl2(PPh3)2 701.89 0.3   21 mg 0.030 CuI 190.44 1.0   22 mg 0.110 Et3N 101.19 6.5  100 &mgr;L 0.72 DMF  2.0 mL

[0881] Resin 1 (145 mg, 0.111 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-ethynylbenzamide 2 (124 mg, 0.288 mmol) and Et3N (100 &mgr;L, 0.72 mmol) in DMF (2.0 mL) was added and the resin agitated for 5 min. A mixture of PdCl2(PPh3)2 (21 mg, 0.030 mmol) and CuI (22 mg, 0.110 mmol) was added and the resin was agitated for 60 h. The resin was drained, washed with DMF (3×2 mL), DCM (3×2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-55%, 0.1% TFA, UV analysis 300 nm, 26 min) and lyophilization of the collected fractions afforded 2.6 mg (5% yield) of N-((2S)-amino-1-hydroxycarbamoyl-ethyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide. LRMS (ES+) m/z 434.0 (C23H23N5O4+H requires 434.19); RP-HPLC (300 nm, 26 min run) 15.3 min.

Synthesis of N-[4-Butadiynyl-benzoyll-Thr(tBu) on Resin (Continued to make Examples 22 and 23)

[0882] 166

[0883] Preparation of (2S, 3R)-2-N-Fmoc-amino-3-tert-butoxy-N-hydroxy-butyramide on hydroxylamine 2-chlorotrityl resin (2). 45 167 168 Reagent MW Eq. g/mL mmol Hydroxylamine resin (1) 0.77 mmol/g 1.0 3.188 g 2.45 Fmoc-Thr(tBu)-OH 397.50 3.0 2.927 g 7.36 HATU 380.25 3.0 2.798 g 7.36 DIEA 129.25 10.0 4.3 mL 24.6 DMF 40 mL

[0884] A suspension of N-Fmoc-hydroxylamine 2-chlorotrityl resin (3.188 g, 2.45 mmol, 0.77 mmol/g, Novabiochem) in DCM (40 mL) was shaken for 2 h and drained. The resin was treated with 20% piperidine in DMF (40 mL) for 1 hour, washed with DMF (2×40 mL), treated a second time with 20% piperidine in DMF (40 mL), washed with DMF (3×40 mL) and DCM (3×40 mL) and drained completely. In a separate flask, Fmoc-Thr(tBu)-OH (2.927 g, 7.36 mmol), HATU (2.798 g, 7.36 mmol) and DIEA (4.3 mL, 24.6 mmol) were dissolved in DMF (40 mL), stirred three minutes and added to the resin. After shaking for 24 h, the mixture was drained, washed with DMF (4×40 mL) and DCM (4×40 mL) and dried in vacuo to give 3.500 g of a yellow resin.

Preparation of 4-buta-1,3-diynyl-N-(2-tert-butoxy-1-hydroxycarbamoyl-propyl)-benzamide on hydroxylamine 2-chlorotrityl Resin (4).

[0885] 46 169 170 Reagent MW Eq. g/mL mmol Fmoc-threonine/resin (2) 0.77 mmol/g 1.0 2.030 g 1.56 Butadiynyl benzoic acid (3) 170.16 2.3 0.617 g 3.63 EDCI 191.71 2.8 0.834 g 4.35 HOBt 135.13 2.8 0.588 g 4.35 DIEA 129.25 3.7 1.0 mL 5.7 DCM 15 mL DMF 4 mL

[0886] The resin 2 (2.030 g, 1.56 mmol, 0.77 mmol/g) was swelled in DCM (20 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (20 mL) for 1 hour, washed with DMF (4×20 mL) and DCM (4×20 mL) and drained completely. In a separate flask, 4-buta-1,3-diynyl-benzoic acid 3 (0.617 g, 3.63 mmol), EDCI (0.834 g, 4.35 mmol), HOBt (0.588 g, 4.35 mmol) and DIEA (1.0 mL, 5.7 mmol) were dissolved in DCM (15 mL) and DMF (4 mL), stirred 45 min and added to the resin. After shaking for 36 h, the mixture was drained, washed with DMF (4×20 mL) and DCM (4×20 mL) and dried in vacuo to give 1.900 g of a pale brown resin.

Synthesis of Diacetylenic Threonine Hydroxamic Acids

Example 22

[0887] (2S,3R)-4-[4-(3-aminomethyl-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide (3). 47 171 172 Reagent MW Eq. g/mL mmol Diacetylene on resin (1) 0.77 mmol/g 1.0 100 mg 0.077 3-Iodobenzylamine HCl (2) 269.51 4.0 83.0 mg 0.308 PdCl2(PPh3)2 701.89 0.2 11.0 mg 0.016 CuI 190.44 0.5 7.0 mg 0.037 Et3N 101.19 23 250 &mgr;L 1.80 DMF 1.5 mL

[0888] Resin 1 (obtained from previous synthesis) (100 mg, 0.077 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 3-iodobenzylamine hydrochloride 2 (83.0 mg, 0.308 mmol) and Et3N (250 &mgr;L, 1.80 mmol) in DMF (1.5 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2(PPh3)2 (11.0 mg, 0.016 mmol) and CuI (7.0 mg 0.037 mmol) were added and the mixture shaken for 36 h. The resin was drained, washed with DMF (4×2 mL), DCM (4×2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.5 mL). The cleavage fractions were combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractions afforded 4.3 mg (14%) of (2S,3R)-4-[4-(3-aminomethyl-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide as a white solid. LRMS (ES+) m/z 392.0 (C22H21N3O4+H requires 392.15); RP-HPLC (300 nm, 28 min run) 10.0 min.

Synthesis of Diacetylenic Benzylamine Analogues

Example 23

[0889] (1S, 2R)-N-2-bydroxy-1-hydroxycarbamoyl-propyl)-4-[4-(4-meorphoin-4-ylmethyl-phenyl)-buta-1,3-diynyl]-benzamide (4) 173

Preparation of Threonine Diacetylenic Benzaldehyde on Resin (3).

[0890] 48 174 175 Reagent MW Eq. g/mL mmol Diacetylene on resin (1) 0.77 mmol/g 1.0 1.00 g 0.770 4-Iodobenzaldehyde 232.00 4.0 715 mg 3.081 PdCl2(PPh3)2 701.89 0.07 40.0 mg 0.057 CuI 190.44 0.13 19.0 mg 0.100 Et3N 101.19 9.3 1.00 mL 7.17 DMF 20.0 mL

[0891] Resin 1 (1.00 g, 0.77 mmol) was pre-swelled in DCM (25 mL) for 14 h and drained. A solution of 4-iodobenzaldehyde 2 (715 mg, 3.08 mmol) and Et3N (1.00 mL, 7.17 mmol) in DMF (20 mL) was purged with N2 for two minutes and added to the resin. After mixing for 5 min, PdCl2(PPh3)2 (40.0 mg, 0.057 mmol) and CuI (19.0 mg, 0.100 mmol) were added and the reaction shaken for 48 h. The resin was drained, washed with DMF (4×20 mL), DCM (4×20 mL) and dried in vacuo to give 1.100 g of a dark yellow resin.

Preparation of (1S, 2R)-N-2-hydroxy-1-hydroxycarbamoyl-propyl)-4-[4-(4-morpholin-4-ylmethyl-phenyl)-buta-1,3-diynyl]-benzamide (4).

[0892] 49 176 177 Reagent MW Eq. mg/&mgr;l mmol Benzaldehyde on resin (3) 0.77 mmol/g 1.0 188 mg 0.141 Morpholine 87.12 6.0 75 &mgr;L 0.860 NaCNBH3 62.84 4.5 40 mg 0.637 Trimethyl orthoformate 106.12  6.5 100 &mgr;L 0.914 Acetic acid 60.05 12.3 100 &mgr;L 1.750 THF 3.0 mL MeOH 1.0 mL

[0893] A solution of morpholine (75 &mgr;L, 0.860 mmol) and trimethyl orthoformate (100 &mgr;L, 0.914 mmol) in THF (3.0 mL) was added to a Teflon-lined screw-capped vial containing the resin-bound diacetylenic benzaldehyde 3. The resin was agitated for 10 min, treated successively with acetic acid (100 &mgr;L, 1.75 mmol) and a solution of NaCNBH3 (40.0 mg, 0.637 nmmol) in MeOH (1.0 mL) and shaken for 44 h. The resin was filtered, washed with DMF (3×3 mL) and DCM (3×3 mL) and drained. Cleavage from the resin was achieved by treatment with 10% TFA/DCM (2.0 mL) and shaking 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (2.0 mL). The cleavage fractions were combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude yellow residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-35%, 0.1% TFA, UV analysis 300 nm, 18 min) and lyophilization of the collected fractions afforded 19.0 mg (29%) of 472 as a fluffy yellow solid. LRMS (ES+) m/z 462.0 (C26H27N3O5+H requires 462.10); HPLC (300 nm, 18 min run) 10.3 min.

Synthesis of 4′-Benzamide Diacetylene Threonine Hydroxamic Acid

Example 24

[0894] (1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide (5) 178

Preparation of N-(2-trityl-amino-ethyl)-4-ethynyl-benzamide (3).

[0895] 50 Reagent MW Eq. g/mL mmol 4-Ethynylbenzoic acid (1) 146.14 1.0 0.292 g 2.00 N-Trityl ethylenediamine 302.41 1.3 0.810 g 2.67 EDCI 191.71 1.0 0.382 g 2.00 HOBt 135.13 3.0 0.270 g 2.00 DIEA 129.25 4.0  1.40 mL 8.00 DMF  10.0 mL

[0896] To a solution of 4-ethynylbenzoic acid 1 (292 mg, 2.00 mmol), EDCI (382 mg, 2.00 mmol), and HOBt (270 mg, 2.00 mmol) in DMF (10 mL) was added N-trityl ethylenediamine 2 (810 mg, 2.67 mmol) and DIEA (1.4 mL, 8.0 mmol). The reaction mixture was stirred 24 h, diluted with EtOAc (200 mL), washed with 0.5 M HCl (60 mL), saturated NaHCO3 (2×60 mL), H2O (4×60 mL), dried over MgSO4 and concentrated to give 836 mg (97% yield) of N-(2-trityl-amino-ethyl)-4-ethynyl-benzamide 3 as a white solid, mp 50-51° C. Rf=0.40 (1:1 Hexanes/EtOAc).

Preparation of (1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide (5).

[0897] 51 Reagent MW Eq. g/mL mmol Alkyne on resin (4) 0.77 mmol/g 1.00  150 mg 0.116 4-Ethynylbenzamide (3) 430.54 3.00  151 mg 0.350 PdCl2(PPh3)2 701.89 0.25   21 mg 0.030 CuI 190.44 1.25   28 mg 0.147 Et3N 101.19 9.50  150 &mgr;L 1.10 DMF  2.0 mL

[0898] Resin 4 (150 mg, 0.116 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-ethynylbenzamide 3 (151 mg, 0.350 mmol) and Et3N (150 &mgr;L, 1.10 mmol) in DMF (2.0 mL) was added and the resin agitated for 5 min. A mixture of PdCl2(PPh3)2 (21 mg, 0.030 mmol) and CuI (28 mg, 0.147 mmol) was added and the resin was agitated for 60 h. The resin was drained, washed with DMF (3×2 mL), DCM (3×2 mIL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2.0 miL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 26 min) and lyophilization of the collected fractions afforded 2.0 mg (4% yield) of (1S,2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-{4-[4-(2-amino-ethylcarbamoyl)-phenyl]-buta-1,3-diynyl}-benzamide. LRMS (ES+) m/z 449.1 (C24H24N4O5 +H requires 449.18); RP-HPLC (300 nmn, 26 min run) 17.0 min.

Synthesis of 3′-Pyridine Diacetylene Threonine Hydroxamic Acid

Example 25

[0899] N-((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3-yl-buta-1,3-diynyl)-benzamide (3) 179

[0900] Preparation of N-((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3-yl-buta-1,3-diynyl)-benzamide 52 Reagent MW Eq. g/mL mmol Alkyne on resin (1) 0.77 mmol/g 1.0  142 mg 0.109 3-Ethynylpyridine (2) 103.12 3.4   38 mg 0.368 PdCl2(PPh3)2 701.89 0.3   22 mg 0.031 CuI 190.44 1.2   25 mg 0.131 Et3N 101.19 13  200 &mgr;L 1.40 DMF  2.0 mL

[0901] Resin 1 (142 mg, 0.109 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 3-ethynylpyridine 2 (38 mg, 0.368 mmol) and Et3N (200 &mgr;L, 1.4 mmol) in DMF (2 mL) was added and the resin agitated for 5 min. A mixture of PdCl2(PPh3)2 (22 mg, 0.031 mmol) and CuI (25 mg, 0.131 mmol) was added and the resin was agitated for 72 h. The resin was drained, washed with DMF (3×2 mL), DCM (3×2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 24 min) and lyophilization of the collected fractions afforded 4.4 mg (11% yield) of N-((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3-yl-buta-1,3-diynyl)-benzamide. LRMS (ES+) m/z 364.0 (C20H17N3O4+H requires 364.13); RP-HPLC (300 nm, 24 min run) 11.2 min.

Example 26

[0902] Synthesis of N-(1-(N-hydroxycarbamoyl)(1S,2R)-2-hydroxy propyl){4-[4-(6-morpholin4-yl(3-pyridyl))buta-1,3-diynyl]phenyl}carboxamide (5) 53 180 181 182 183 Reagent MW EQ g/ml mmol Dibromovinylbenzoic acid (1) 320 1.0 9.6 g 30.0 2-Chloro-5-ethynyl-pyridine 138 1.3 5.43 g 39.0 Pd2dba3 915 0.01 274 mg 0.3 (1% cat.) TMPP 352 0.04 422 mg 1.2 (4%) TEA 101 3.0 12.5 ml 90.0 DMF 90 ml degassed with argon

Preparation of 4-[4-(6Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester

[0903] 184

[0904] 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid was made according to the method of Wang Shen and Sheela A. Thomas in Org.Lett. 2000, 2(18), 2857-2860.

[0905] A solution of 4-(2,2-dibromo-vinyl)-benzoic acid methyl ester (1) (9.6 g, 30.0 mmol), ethynyl-pyridine (2) (5.43 g, 39.0 mmol), Pd2dba3 (274 mg, 0.3 mmol), tris(4-methoxyphenyl) phosphine (TMPP) (422 mg, 1.2 mmol) were dissolved in argon sparged (5 min.) DMF (60 ml). The reaction was sparged with argon for 1 min. TEA (12.5 ml, 90.0 mmol) was added to the stirred reaction mixture that was then heated under argon at 85° C. for 3 hours. The reaction was found complete by LCMS. The reaction was cooled to rt and diluted with EtOAc/hexane (1:1) (500 ml). The organic phase was washed with 1 M NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (1:1). The fractions with product were evaporated to give 9.06 g of product in good purity (˜96% pure). The material was taken on without further purification.

Preparation of 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic Acid (3)

[0906] A 6M aq. solution of NaOH (15 ml) was added to a stirred solution of 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester. (9.06 g, 30 mmol) in MeOH (350 ml) at rt. The reaction solution was heated to reflux for 3 hours. The reaction stayed a mixture and did not turn clear. HPLC and LCMS indicated that the reaction was forming side products. The reaction was cooled to rt and some MeOH (˜200 ml) was removed by evaporation under reduced pressure. Water (400 ml) was added to the mixture. Conc. HCl was added dropwise to the stirred solution until acidic by pH paper (pH2). The yellow precipitate that formed was collected by suction filtration. The solid was washed with water (3×20 ml) and hexane (2×20 ml) to give the crude product. HPLC indicated that there was approximately 40% product in the mixture. The crude reaction product was purified by flash chromatography using EtOAc (8-10%)/hexane as eluant. The pure fractions were evaporated and dried in vacuo to give 4.2 g of product 3 in 50% yield.

Preparation of [4-[4-(6-chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoyl]-HN-Thr(OtBu)-hydroxamic acid trityl resin (4)

[0907] 185

4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-beiizoic acid (3) was coupled to a tert-butyl protected threonine pre-loaded on hydroxylamine 2-chlorotrityl resin following the same procedure as used for Example 26. The coupling employed DIC and HOBT. [N-Fmoc-hydroxylamine 2-chlorotrityl resin was purchased from Novabiochem cat.# 01-64-0165.]

Preparation of N-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-[4-(6-morpholin-4-yl-pyridin-3-yl)-buta-1,3-diynyl]-benzamide (5)

[0908] 186

[0909] A solution of morpholine (300 uL) in NMP (1 ml) was added to a vial containing the 2-cloropyridine resin (4) (150 mg, 0.12 mmol). The reaction mixture was purged with argon and heated to 85-90° C. for 24 hours. The resin was drained and washed with DMF and DCM alternately several times. The product was cleaved from the resin through treatment with a TFA/water solution (80:20) (1.5 ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80:20) (0.5 ml). The combined TFA and organic fractions were diluted with CH3CN/water (1:1) (10 ml), water (2 ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (1 ml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness to give 2.2 mg of pure product as the TFA salt (˜32% yield).

Example 27

[0910] Synthesis of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide (4) 187

[0911] Preparation of 2- {4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonyloxy-butyric hydroxamic acid trityl resin (3). 54 188 189 190 Reagent MW EQ g/ml mmol H-Thr(Boc)-NHO-Trt Resin (1) 1.0 5.8 g 4.47 1,3-diynyl benzoic acid (2) 261.3 1.4 1.64 g 6.25 HOBT 135.1 1.4 0.85 g 6.25 DIC 126.2 1.4 0.98 ml 6.25 DIEA 129.25 3.5 2.7 ml 15.6 DMF 50 ml

[0912] DIEA (2.7 ml, 15.6 mmol) was added to a stirred solution of 4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoic acid (2) (1.64 g, 6.3 mmol), HOBT (0.85 g, 6.3 mmol), DIC (0.98 ml, 6.3 mmol) in DMF (50 ml). After 2 min., the Thr hydroxylamine resin (5.8 g, 4.5 mmol) was added in one portion. [N-Fmoc-hydroxylamine 2-chiorotrityl resin was purchased from Novabiochem cat.# 01-64-0165.] After 12 hours at rt, the reaction was found complete by LCMS. The resin was drained and washed with DMF and DCM alternately 3 times each. The product on resin 3 was used as is in subsequent reactions without further treatment.

Preparation of 4-]4-(4-Ainino-phenyl)-buta-1,3-diynyl]-N-(2-hydroxy-1-hydroxy carbamoyl-propyl)-benzamide (4)

[0913] 55 191 192 Reagent MW EQ g/ml mmol 1,3-diynyl benzoic Tbr Resin (3) 1.0 120 mg 0.09 TFA/water (80:20) 1.5 ml

[0914] The product (4) (120 mg, 0.09 mmol) was cleaved from the resin through treatment with a TFA/water solution (80:20) (1.5 ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80:20) (0.5 ml). The combined TFA and organic fractions were diluted with CH3CN/water (1:1) (10 ml), water (2 ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (1 ml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness to give 2.2 mg of pure product as the TFA salt. The product (4) was lyophilized again from CH3CN/water with 10 equivalents of HCl to remove most of the TFA to yield 2 mg of product as the HCl salt (˜53% yeild).

Example 28

[0915] Synthesis of 4-{4-[4-(2-Dimethylamino-acetylamino)-phenyl]-buta-1,3-diynyl}-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide (6) (Continued from Compound 3 of Example 27 Above) 193

Preparation of 2-{4-(4-[4-(2-Bromo-acetylamino)-phenyl]-buta-1,3-diynyl}-benzoylamino)-3-tert-butoxycarbonyloxy-butyric acid hydroxamate trityl resin (5).

[0916] 56 194 195 Reagent MW EQ g/ml mmol Amino 1,3-diynyl benzoic Thr 1.0 0.75 g 0.578 Trt Resin (3) Bromo-acetyl chloride 157.4 8.0 0.728 g 4.62 Lutidine 107 10.0 1.07 ml 9.24 DMF 6 ml

[0917] A solution of bromo-acetyl chloride (0.75 g, 0.58 mmol) in DCM (2 ml) was added to a mixture of 2- {4-[4-(4-Amino-phenyl)-buta-1,3-diynyl]-benzoylamino}-3-tert-butoxycarbonyloxy-butyric acid hydroxamate Trt Resin (3) (0.75 g, 0.58 mmol), lutidine (1.1 ml, 9.2 mmol) and DCM (4 ml) at rt with shaking. After shaking for 1.5 hours, the reaction was found complete by LCMS. The resin was drained and washed with DCM (2×10 ml), DMF (3×10 ml) and DCM (3×10 ml) again. The resin was drained and dried in vacuo. The product on resin 5 was used as is in subsequent reactions without further treatment.

Preparation of 4-{4-[4-(2-Dimethylamino-acetylamino)-phenyl]-buta-1,3-diynyl}-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide (6).

[0918] 57 196 197 Reagent MW EQ g/ml mmol Bromo acetic Thr Trt Resin (5) 1.0 125 mg 0.093 Dimethyl amine 45.08 0.2 ml excess NMP 1.2 ml

[0919] A solution of dimethyl amine (0.2 ml) in NMP (1.2 ml) was added to bromo acetic Thr Trt Resin (5) (125 mg, 0.09 mmol) at rt with shaking. After shaking for 12 hours, the reaction was found complete by LCMS. The resin was drained and washed with DCM (2×10), DMF (3×10) and DCM (3×10) again. The product (6 ml) was cleaved from the resin through treatment with a TFA/water solution (80:20) (1.5 ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80:20) (0.5 ml). The combined TFA and organic fractions were diluted with CH3CN/water (1:1) (10 ml), water (2 ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (1 ml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness to give 2 mg of pure product as the TFA salt (˜37% yeild).

Example 29

[0920] Synthesis of 4-{4-[4-(2-Amino-4-methyl-pentanoylamino)-phenyl]-buta-1,3-diynyl}-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide (7) (Continued from Compound 3 of Example 27 Above) 58 198 199 Reagent MW EQ g/ml mmol Amino 1,3-diynyl benzoic Thr Trt 1.0 125 mg 0.093 Resin (3) Fmoc-L-leucine 353.42 4.0 0.135 g 0.384 HATU 380 4.0 0.146 g 0.384 DIEA 129.25 8.0 133 ul 0.768 DMF 1.5 ml

[0921] A solution of Fmoc-L-leucine (0.135 g, 0.38 mmol), HATU (0.146 g, 0.38 mmol) in DMF (1.5 ml) was made. After 2 min. of shaking, the activated acid was added to the amino 1,3-diynyl benzoic Thr Trt Resin (3) (125 mg, 0.09 mmol) at rt with shaking. After shaking for 36 hours, the reaction was drained and washed with DCM (2×4 ml), DMF (3×4 m1) and DCM (3×4 ml) again. The resin was treated with 20% piperizine in DMF (4 ml ) for 2 hours twice. The resin was drained and washed with DMF and DCM alternately several times. The product was cleaved from the resin through treatment with a TFA/water solution (80:20) (1.5 ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80:20) (0.5 ml). The combined TFA and organic fractions were diluted with CH3CN/water (1:1) (10 ml), water (2 ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (1 ml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20×50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness to give 1.7 mg of pure product (7) as the TFA salt (˜30% yield).

Examples 30-1307 of Table 1 were Synthesized According to the Synthetic Schemes Described Above.

Biological Protocols and Data

[0922] P. aeruginosa LpxC Inhibition Assay

[0923] The assay followed the general method of Hyland et al (Journal of Bacteriology 1997 179, 2029-2037: Cloning, expression and purification of UDP-3-O-acyl-GlcNAc deacetylase from Pseudomonas aeruginosa: a metalloamidase of the lipid A biosynthesis pathway) and the radiolabeling procedure is according to Kline et al. supra. Briefly, samples were incubated with 2 nM P. aeruginosa LpxC and 150 nM [3H-Ac]-UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc in a total volume of 50 uL for 90 min at room temperature. Reactions were carried out in 96-well polypropylene plates in 50 mM sodium phosphate buffer, pH 7.5, containing 1 mg/mL BSA. Reactions were stopped by the addition of 180 uL of a 3% suspension of activated charcoal powder in 100 mM sodium acetate, pH 7.5. Supernatants were clarified by centrifugation. A portion of the clarified supernatant, containing the enzymatically released [3H]-acetate, was transferred to opaque white 96-well plates containing scintillation fluid. The radioactivity was measured in a Perkin-Elmer/Wallac Trilux Microbeta counter. Control reactions to which 5 mM EDTA had been added were included with each run to determine nonspecific tritium release.

[0924] Bacterial Screens and Cultures

[0925] Bacterial isolates were cultivated from −70° C. frozen stocks by two consecutive overnight passages at 35° C. in ambient air on 5% blood agar (Remel, Lenexa, Kans.). Clinical isolates tested were from a collection composed of isolates collected during clinical trials and recent clinical isolates obtained from various geographically diverse hospitals in the US. Quality control and primary panel strains were from the American Type Culture Collection (ATCC; Rockville, Md.), with the exception of P. aeruginosa PAO200, a strain with a deletion of the mexABoprM genes that was received from Dr. H. Schweizer. This strain does not express the principal multidrug efflux pump and is hypersusceptible to many antibacterials. Strain Z61 (ATCC 35151) is also hypersusceptible to antibacterials. It is thought that the hypersusceptibility of this strain is the result of increased permeability of its outer membrane (Angus B L et al, Antimicrobial Agents and Chemotherapy 1982 21, 299-309: Outer membrane permeability in Pseudomonas aeruginosa: Comparison of a wild-type with an antibacterial-supersusceptible mutant).

[0926] Susceptibility Testing

[0927] Minimum Inhibitory Concentrations (MICs) were determined by the broth microdilution method in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) guidelines. In brief, organism suspensions were are adjusted to a 0.5 McFarland standard to yield a final inoculum between 3×105 and 7×105 colony-forming units (CFU)/mL. Drug dilutions and inocula were made in sterile, cation adjusted Mueller-Hinton Broth (Remel). An inoculum volume of 100 &mgr;l was added to wells containing 100 &mgr;l of broth with 2-fold serial dilutions of drug. All inoculated microdilution trays were incubated in ambient air at 35° C. for 18-24 hours. Following incubation, the lowest concentration of the drug that prevented visible growth was recorded as the MIC. Performance of the assay was monitored by the use of laboratory quality-control strains against tobramycin, that has a defined MIC spectrum, in accordance with NCCLS guidelines.

Efficacy in Mouse Model of Systemic Pseudomonas aeruginosa Infection

[0928] Female Balbic mice were injected intraperitoneally with 0.5 ml of a bacterial suspension containing approximately 100 times the dose that would kill 50% of animals (LD50) of P. aeruginosa strain PAO1 or E. coli ATCC 25922. At one and five hours post infection, the test compound was injected intravenously in doses ranging from 5 mg/kg to 100 mg/kg, five mice per group. Mice were observed for 5 days, and the dose of compound resulting in survival of 50% of mice (ED50) was calculated.

Drug Combination (Synergy) Studies

[0929] I. Principle

[0930] Checkerboard experiments can be performed to assess potential interactions between primary drug of interest (#1) and other related antibacterials (#2). P. aeruginosa ATCC 27853, S. aureeus ATCC 29213 and other organisms can be used as challenge strains as well as selected clinical isolates. Broth microdilution format can be used to assess the activity of drug #1 and test compound alone and in combination. Two-fold dilutions of the two compounds to be tested (each bracketing the expected MIC value) are used. The fractional inhibitory concentration (FIC) was calculated as the MIC of compound #1 in combination with a second compound, divided by the MIC of compound #1 alone. A summation FIC (&Sgr;FIC) was computed for each drug combination as the sum of the individual FICs of compound #1 and #2. Synergy was defined as an &Sgr;FIC ≦0.5, indifference as an &Sgr;FIC between 0.5 and 4, and antagonism as &Sgr;FIC>4. The lowest &Sgr;FIC was used for the final interpretation of drug conbination studies.

[0931] Interpretation of summation (&Sgr;FIC)

[0932] a) Synergism, x≦0.5

[0933] b) Indifference, 0.5<x≦4

[0934] c) Antagonism, x>4 59 TABLE 2 Demonstration of Antibacterial activity of Select Compounds from Table 1 Enzyme inhibitory activity Compound Example # IC50 (nM) 12 <100 nM 572 <100 nM 481 <100 nM 19 <100 nM 516 <100 nM 280 <100 nM 366 <100 nM 777 <100 nM 315 <100 nM 779 <100 nM 860 <100 nM 801 <100 nM 13 <100 nM

[0935] 60 TABLE 3 Antibacterial activity vs standard panel of organisms (MIC, &mgr;g/ml). Bacterial strain: Compound P. aeruginosa E. coli S. aureus hyper-permeable P. aeruginosa Example # 27853 25922 29213 P. aerug. 35151 PAO200 mexAB  12 A A C A A 572 A A C A A 481 A A C A A  19 A A B A A 516 A A C A A 280 A A C A A 366 A A C A A 777 A A C A A 315 A A C A A 779 A A C A A 860 A A C A A 801 A A C A A  13 A A C AA A MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C

[0936] 61 TABLE 4 Antibacterial activity vs cystic fibrosis isolates of Pseudomonas aeruginosa (MIC, &mgr;g/ml). Strains have the following phenotypes: 3198 and 3236, sensitive to most antibacterials; 2196, resistant to ciprofloxacin; 3224, resistant to ceftazidime; 3317, resistant to aztreonam; 1145 and 3206, multi-drug resistant. Strain number: 3198 3236 2196 3224 3232 3317 1145 3206 Phenotype: Sensitive Sensitive Cipro R Tobra R Ceftaz. R Aztr. R MDR MDR LpxC inhibitors  12 A A B A A A A A 481 A A A A A A A A  19 A A A A A A A A 516 A A A A A A A A 280 A A B A A A A A 366 A A A A A A A A 777 A A A A A A A A 315 A A A A A A A A 779 A A A A A A A A 801 A A A A A A A A  13 A A A A A A A A Comparator antibacterials Tobramycin 2 0.5 2 64 1 2 8-32 64 Aztreonam 1 0.5 1 1 1 64 >128 >128 Ceftazidime 2 0.25 2 2 64 4 >128 >128 Cefepime 4 2 2 8 2 8 >128 32 Ciprofloxacin 1 0.06 >8 2 2 0.5 4 >8 MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C

[0937] 62 TABLE 5 Antibacterial activity vs non-CF clinical isolates of P. aeruginosa and vs other gram- negative pathogens. Set 1: non-fermenting organisms. P. aer., P. aeruginosa; Acinet. calc., Acinetobacter calcoaceticus; Alcal. xyl., Alcaligenes xylosoxidans; B. cep., Burkholderia cepacia; S. malt., Stenotrophomonas maltophilia Species: P. aer. P. aer P. aer 27853 PAO1 P. aer 12307 psa-6b Acinet. calc. Alcal. xyl B. cepacia S. malt. LpxC inhibitors  12 A A A A A A B A 481 A A A A C C B C  19 A A A A A B B B 516 A A A C C C C 280 A A A A C B B B 366 A A A B C A B B 777 A A B A B A C 315 A A A A C B A A 779 A A A C A A B 801 A A A B C B C  13 A A A C A A B Comparator antibacterials Tobramycin 8 2 2 64    64/>128 0.5 Aztreonam 16 32 32 32 64 >128/16    Ceftazidime 4 64 16 1 8/4 1 Cefepime 2 8 8 8 32/16 8/1 Meropenem 0.5 0.25 4 0.5 4 64 Pip/Tazo 4 >128 8 1 64 16 Ciprofloxacin 0.5 2 0.5 0.5 MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C

[0938] 63 TABLE 6 Antibacterial activity vs non-CF clinical isolates of P. aeruginosa and vs other gram- negative pathogens, continued. Set 2: enteric organisms. E. aer., Enterobacter aerogenes; E. clo., Enterobacter cloacae; E. coli, Escherichia coli; K. pneu., Klebsiella pneumoniae; K. oxy., Klebsiella oxytoca; P. mir., Proteus mirabilis; S. marc., Serratia marcescens. Species: E. aer. E. clo. E. coli 1619 E. coli 2788 K. pneu. K. oxy. P. mir. S. marc. LpxC inhibitors  12 C A A A A A A A 481 C A A A A A A A  19 A A A A A A A A 516 C B A B C C C A 280 C A A A B C B B 366 C A A A B B A A 777 B A A A A A A A 315 C A A A C C C B 779 C A A A B B B A 801 B A A A A A A A  13 C A A A A A A A Comparator antibacterials Tobramycin 64 0.06 16/64 0.06/2   64 1 2 2 Aztreonam <=0.13 128/64  <=0.13/0.25     2 0.5 <=0.13 <=0.13 Ceftazidime 32 0.25 >128     0.25/<=0.13 8 0.25 <=0.13 0.25 Cefepime <=0.13       4/<=0.13 <=0.13 8 <=0.13 <=0.13 <=0.13 Meropenem 2 <=0.06 0.25/0.13 <=0.06 0.13 <=0.06 0.5 0.13 Pip/Tazo 2 >128 1 >128 2 0.25 1 Ciprofloxacin >8 0.015 2 0.03 0.06 0.03 0.03 0.25 MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C

[0939] 64 TABLE 7 Drug Combination (Synergy) Studies Result Minimum Concentration (mg/ml) required to inhibit grouth of E. coli 25922 Erythromycin LpxC inhibitor 925 LpxC inhibitor 925 only — 6.25 Erythromycin only 128 — LpxC inhibitor 925  2 0.78 +erythromycin

[0940] Each of the Example compounds of Table 1 was synthesized and assayed as described above. Many of the Example compounds 1-1307 displayed an IC50 value of less than 10 &mgr;M with respect to LpxC. Many of these compounds displayed an IC50 value of less than or equal to 1 &mgr;M or less than or equal to 0.1 &mgr;M. Many of these compounds exhibited IC50 values of less than or equal to 0.050 &mgr;M, less than or equal to 0.030 &mgr;M, less than or equal to 0.025 &mgr;M, or less than or equal to 0.010 &mgr;M.

[0941] It should be understood that the organic compounds according to the invention may exhibit the phenomenon of tautomerism. As the chemical structures within this specification can only represent one of the possible tautomeric forms, it should be understood that the invention encompasses any tautomeric form of the drawn structure. 65 TABLE 1 Example Structure Name MH+ 30 200 3,4-difluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 275.2 31 201 (2S,3R)-N,3-dihydroxy-2-[(4- phenylbutanoyl)amino]butanamide 281.3 32 202 (2S,3R)-N,3-dihydroxy-2-({4-[4- (methyloxy)phenyl]butanoyl}amino)butanamide 311.3 33 203 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- phenylpentanamide 295.3 34 204 (2E,4E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- phenylpenta-2,4-dienamide 291.3 35 205 (2E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3- phenylprop-2-enamide 265.3 36 206 (2S,3R)-3-hydroxy-2-({(2E)-3-[4- (methyloxy)phenyl]prop-2- enoyl}amino)butanoic acid 280.3 37 207 (3R)-3-amino-N-((1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- phenylpentanamide 310.4 38 208 (2E)-3-(4-fluorophenyl)-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}prop- 2-enamide 283.3 39 209 (2E)-3-(3-bromophenyl)-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}prop- 2-enamide 344.2 40 210 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(2- phenylethyl)amino]methyl}benzamide 372.4 41 211 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(4- phenylbutyl)amino]methyl}benzamide 400.5 42 212 4-[(cyclopropylanimo)methyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 308.3 43 213 4-[(hexylamino)methyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 352.4 44 214 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(2- pyridin-2-ylethyl)amino]methyl}benzamide 373.4 45 215 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4- methylpiperazin-1-yl)benzamide 337.4 46 216 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (piperidin-1-ylmethyl)benzamide 336.4 47 217 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (morpholin-4-ylmethyl)benzamide 338.4 48 218 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({[3-(2-oxopyrrolidin-1- yl)propyl]amino}methyl)benzamide 393.5 49 219 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[(3-phenylpropyl) amino]methyl}benzamide 386.5 50 220 (2S,5R)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- phenylpyrrolidine-2-carboxamide 308.3 51 221 (2R,5S)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- phenylpyrrolidine-2-carboxamide 308.3 52 222 (2S,3R)-2-{[(3S)-3-amino-4- phenylbutanoyl]amino}-N,3- dihydroxybutanamide 296.3 53 223 (2S,3R)-2-{[(2S)-2-amino-4- phenylbutanoyl]amino}-N,3- dihydroxybutanamide 296.3 54 224 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6-(2- pyrrolidin-1-ylethyl)pyridine-3- carboxamide 337.4 55 225 2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxy-3- methylbutanoic acid 342.4 56 226 2-{[4-(4-ethylphenyl)phenyl]carbonylamino}-3-hydroxy-4- methylpentanoic acid 356.4 57 227 {[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}(thien-2- yl)acetic acid 366.5 58 228 N-(2-{[(1,1-dimethylethyl)oxy]amino}-2-oxo- 1-thien-2-ylethyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 437.6 59 229 3-(dimethylamino)-2-{[(4′-ethyl-1,1′-biphenyl- 4-yl)carbonyl]amino}propanoic acid 341.4 60 230 4′-ethyl-N-{(1S)-1-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]-3-methylbutyl}-1,1′- biphenyl-4-carboxamide 456.6 61 231 4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-2- oxo-1-(phenylmethyl)ethyl]-1,1′- biphenyl-4-carboxamide 490.6 62 232 (2S)-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}pyrrolidine- 2-carboxamide 440.5 63 233 4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-1- (1H-imidazol-4-ylmethyl)-2-oxoethyl]-1,1′- biphenyl-4-carboxamide 480.5 64 234 (3S)-2-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,2,3,4- tetrahydroisoquinoline-3-carboxamide 502.6 65 235 (2S)-2-[(1,1′-biphenyl-4-ylacetyl)amino]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- methylpentanamide 442.5 66 236 (2S,3R)-2-({(2S)-2-[(1,1′-biphenyl-4- ylacetyl)amino]-3-phenylpropanoyl}amino)- N,3-dihydroxybutanamide 476.5 67 237 (2S,3R)-2-{[(2S)-2-[(1,1′-biphenyl-4- ylacetyl)amino]-3-(4- hydroxyphenyl)propanoyl]amino}-N,3- dihydroxybutanamide 492.5 68 238 (2S)-1-(1,1′-biphenyl-4-ylacetyl)-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}pyrrolidine- 2-carboxamide 426.5 69 239 (2S,3R)-2-{[(2S)-2-[(1,1′-biphenyl-4- ylacetyl)amino]-3-(1H-imidazol-4- yl)propanoyl]amino}-N,3- dihydroxybutanamide 466.5 70 240 (2S)-2-[(1,1′-biphenyl-4-ylacetyl)amino]- N˜1˜-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}pentanediamide 457.5 71 241 (3S)-3-[(1,1′-biphenyl-4-ylacetyl)amino]-4- ({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)- 4-oxobutanoic acid 444.5 72 242 (2S,4R)-1-[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]-4-hydroxy-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}pyrrolidine- 2-carboxamide 456.5 73 243 N-[(1S)-1-(aminomethyl)-2-({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)-2- oxoethyl]-4′-ethyl-1,1′-biphenyl-4- carboxamide 429.5 74 244 4′-ethyl-N-{(1S)-1-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]but-3-ynyl}-1,1′- biphenyl-4-carboxamide 438.5 75 245 (2S,3R)-2-({(2S)-2-[(1,1′-biphenyl-4- ylacetyl)amino]propanoyl}amino)-N,3- dihydroxybutanamide 400.4 76 246 (2S,4R)-1-(1,1′-biphenyl-4-ylacetyl)-4- hydroxy-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}pyrrolidine-2-carboxamide 442.5 77 247 4′-ethyl-N-{(1R,2R)-2-hydroxy-1- [(hydroxy{[(2-hydroxyethyl) amino]carbonyl}amino)methyl]propyl}-1,1′-biphenyl-4-carboxamide 416.5 78 248 N-((2R,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxybutyl)-N- hydroxymorpholine-4-carboxamide 442.5 79 249 N-((2R,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxybutyl)-N- hydroxy-4-methylpiperazine-1-carboxamide 455.6 80 250 N-((1R,2R)-1- {[[(cyclopropylamino)carbonyl](hydroxy) amino]methyl}-2-hydroxypropyl)- 4′-ethyl-1,1′-biphenyl-4-carboxamide 412.5 81 251 4-ethyl-N-{(1R,2R)-2-hydroxy-1- [(hydroxy{[(pyridin-3- ylmethyl)amino]carbonyl}amino) methyl]propyl}-1,1′- biphenyl-4-carboxamide 463.5 82 252 4′-ethyl-N-{(1R,2R)-2-hydroxy-1- [(hydroxy{[(2-pyridin-2-ylethyl)amino]carbonyl}amino)methyl]propyl}1,1′-biphenyl-4-carboxamide 477.6 83 253 4-ethyl-N-{(1R,2R)-2-hydroxy-1- [(hydroxy{[(4-morpholin-4-ylphenyl) amino]carbonyl}amino)methyl]propyl}- 1,1′-biphenyl-4-carboxamide 533.6 84 254 N˜1˜-((2R,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-hydroxybutyl)-N˜1˜- hydroxypiperidine-1,4-dicarboxamide 483.6 85 255 4′-ethyl-N-[2-(hydroxyamino)ethyl]-1,1- biphenyl-4-carboxamide 285.4 86 256 N-{2-[(aminocarbonyl)(hydroxy)amino]ethyl}- 4′-ethyl-1,1′-biphenyl-4-carboxamide 328.4 87 257 N-{2-[(aminocarbonothioyl) (hydroxy)amino]ethyl}- 4′-ethyl-1,1′-biphenyl-4-carboxamide 344.4 88 258 N-{2-[({[2-(dimethylamino) ethyl]amino}carbonyl)(hydroxy) amino]ethyl}4-ethyl-1,1′-biphenyl- 4-carboxamide 399.5 89 259 N-{2-[{[(2-cyanaethyl) amino]carbonyl}(hydroxy)amino]ethyl}4′-ethyl-1,1′- biphenyl-4-carboxamide 381.4 90 260 4′-ethyl-N-[2-(hydroxy{[(2- hydroxyethyl)amino]carbonyl}amino)ethyl]- 1,1′-biphenyl-4-carboxamide 372.4 91 261 N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N- hydroxymorpholine-4-carboxamide 398.5 92 262 N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxy-4- methylpiperazine-1-carboxamide 411.5 93 263 N˜1˜-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N˜1˜- hydroxypiperidine-1,4-dicarboxamide 439.5 94 264 N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N- hydroxypyrrolidine-1-carboxamide 382.5 95 265 N-{2-[[(cyclopropylamino) carbonyl](hydroxy)amino]ethyl}4-ethyl-1,1′-biphenyl-4-carboxamide 368.4 96 266 4′-ethyl-N-{2-[hydroxy({[2- (methyloxy)ethyl]amino}carbonyl) amino]ethyl}-1,1′- biphenyl-4-carboxamide 386.5 97 267 N-{2-[({[2-(acetylamino)ethyl]amino}carbonyl)(hydroxy) amino]ethyl}-4′-ethyl-1,1′- biphenyl-4-carboxamide 413.5 98 268 4′-ethyl-N-{2-[hydroxy({[3-(2- oxopyrrolidin-1-yl)propyl]amino}carbonyl)amino]ethyl}-1,1′- biphenyl-4-carboxamide 453.6 99 269 4′-ethyl-N-[2-(hydroxy{[(3- hydroxypropyl)amino]carbonyl}amino) ethyl]-1,1′-biphenyl-4-carboxamide 386.5 100 270 4′-ethyl-N-{2-[hydroxy({[3- (methyloxy)propyl]amino}carbonyl)amino]ethyl}-1,1′-biphenyl-4-carboxamide 400.5 101 271 N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxy-1,4′- bipiperidine-1′-carboxamide 479.6 102 272 4′-ethyl-N-[2-(hydroxy{[(2-pyridin-2- ylethyl)amino]carbonyl}amino)ethyl]- 1,1′-biphenyl-4-carboxamide 433.5 103 273 4′-ethyl-N-[2-(hydroxy{[(pyridin-3- ylmethyl)amino]carbonyl}amino)ethyl]-1,1′- biphenyl-4-carboxamide 419.5 104 274 4′-ethyl-N-[2-(hydroxy{[(4-morpholin-4- ylphenyl)amino]carbonyl}amino)ethyl]-1,1′- biphenyl-4-carboxamide 489.6 105 275 N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N,3- dihydroxypiperidine-1-carboxamide 412.5 106 276 N-{2-[{[(3-aminocyclohexyl) amino]carbonyl}(hydroxy)amino]ethyl}-4′-ethyl-1,1′-biphenyl- 4-carboxamide 425.5 107 277 N-{2-[{[(2-aminoethyl)amino]carbonyl}(hydroxy)amino]ethyl}- 4′-ethyl-1,1′-biphenyl-4-carboxamide 371.4 108 278 N-{2-[{[(3-aminopropyl)amino]carbonyl}(hydroxy)amino]ethyl}-4′- ethyl-1,1′-biphenyl-4-carboxamide 385.5 109 279 1,1-dimethylethyl 3-({[(2-{[(4′-ethyl-1,1′- biphenyl-4-yl)carbonyl]amino}ethyl)(hydroxy)amino]carbonyl}amino)propylcarbaniate 485.6 110 280 4′-ethyl-N-{2-[({[(4- fluorophenyl)methyl]amino}carbonyl) (hydroxy)amino]ethyl}-1,1′- biphenyl-4-carboxamide 436.5 111 281 N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N-hydroxy-3- [(trifluoroacetyl)amino]pyrrolidine-1- carboxamide 493.5 112 282 N-{2-[{[(4-aminothien-3- yl)amino]carbonyl}(hydroxy)amino]ethyl}- 4′-ethyl-1,1′-biphenyl-4-carboxamide 425.5 113 283 4′-ethyl-N-(2-{hydroxy[(piperidin-3- ylamino)carbonyl]amino}ethyl)-1,1′- biphenyl-4-carboxamide 411.5 114 284 4′-ethyl-N-(2-{hydroxy[(piperidin-4- ylamino)carbonyl]amino}ethyl)-1,1′- biphenyl-4-carboxamide 411.5 115 285 4′-ethyl-N-[2-(hydroxy{[(piperidin-2- ylmethyl)amino]carbonyl}amino)ethyl]- 1,1′-biphenyl-4-carboxamide 425.5 116 286 4′-ethyl-N-[2-(hydroxy{[(piperidin-3- ylmethyl)amino]carbonyl}amino)ethyl]- 1,1′-biphenyl-4-carboxamide 425.5 117 287 3-amino-N-(2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}ethyl)-N- hydroxypyrrolidine-1-carboxamide 397.5 118 288 1,1-dimethylethyl 3-[({[(2-{[(4′-ethyl-1,1′- biphenyl-4-yl)carbonyl]amino}ethyl)(hydroxy)amino]carbonyl}amino)methyl]piperidine-1-carboxylate 525.7 119 289 1,1-dimethylethyl 1-{[(2-{[(4′-ethyl-1,1′- biphenyl-4-yl)carbonyl]amino}ethyl)(hydroxy)amino]carbonyl}pyrrolidin-3-ylcarbamate 497.6 120 290 4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2- (hydroxyarnino)ethyl]amino}carbonyl)propyl]- 1,1′-biphenyl-4-carboxamide 386.5 121 291 N-{(1S,2R)-1-[({2- [(aminocarbonyl)(hydroxy)amino]ethyl}amino)carbonyl]-2-hydroxypropyl}-4′- ethyl-1,1′-biphenyl-4-carboxamide 429.5 122 292 N-{(1S,2R)-1-[({2-[(aminocarbonothioyl) (hydroxy)amino]ethyl}amino) carbonyl]-2-hydroxypropyl}-4′-ethyl-1,1′- biphenyl-4-carboxamide 445.6 123 293 4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2- (hydroxy{[(2-hydroxyethyl)amino]carbonyl}amino)ethyl]amino}carbonyl) propyl]-1′-biphenyl-4- carboxamide 473.5 124 294 4′-ethyl-N-{(1S)-6-hydroxy-1-[(1R)-1- hydroxyethyl]-2,7-dioxo-11-oxa-3,6,8- triazadodec-1-yl}-1,1′-biphenyl-4- carboxamide 487.6 125 295 4′-ethyl-N-{(1S)-6-hydroxy-1-[(1R)-1- hydroxyethyl]-11-methyl-2,7-dioxo-3,6,8,11- tetraazadodec-1-yl}-1,1′-biphenyl-4- carboxamide 500.6 126 296 4′-ethyl-N-{(1S)-6-hydroxy-1-[(1R)-1- hydroxyethyl]-2,7,12-trioxo-3,6,8,11- tetraazatridec-1-yl}-1,1′-biphenyl-4- carboxamide 514.6 127 297 4′-ethyl-N-{(1S,2R)-2-hydroxy-1-[({2- [hydroxy({[3-(2-oxopyrrolidin-1-yl) propyl]amino}carbonyl)amino]ethyl}amino)carbonyl]propyl}-1,1′-biphenyl-4- carboxamide 554.7 128 298 N-{(1S,2R)-1-[({2-[{[(2- cyanoethyl)aminolcarbonyl}(hydroxy)amino]ethyl}amino)carbonyl]-2-hydroxypropyl}-4′- ethyl-1,1′-biphenyl-4-carboxamide 482.6 129 299 N-{(1S,2R)-1-[({2-[[(cyclopropylamino) carbonyl](hydroxy)amino]ethyl}amino)carbonyl]-2-hydroxypropyl}-4′- ethyl-1,1′-biphenyl-4-carboxamide 469.6 130 300 N-{2-[((2S,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3- hydroxybutanoyl)amino]ethyl}-N- hydroxypyrrolidine-1-carboxamide 483.6 131 301 N-{2-[((2S,3R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3- hydroxybutanoyl)amino]ethyl}-N- hydroxymorpholine-4-carboxamide 499.6 132 302 N-{2-[((2S,3R)-2-{[(4′-ethyl-1,1-biphenyl-4- yl)carbonyl]amino}-3- hydroxybutanoyl)amino]ethyl}-N-hydroxy- 4-methylpiperazine-1-carboxamide 512.6 133 303 4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2- (hydroxy{[(pyridin-3-ylmethyl)amino]carbonyl}amino)ethyl]amino}carbonyl)propyl]-1,1′-biphenyl-4- carboxamide 520.6 134 304 4′-ethyl-N-[(1S,2R)-2-hydroxy-1-({[2- (hydroxy{[(2-pyridin-2-ylethyl) amino]carbonyl}amino)ethyl]amino}carbonyl)propyl]-1,1′-biphenyl-4- carboxamide 534.6 135 305 3-chloro-N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(trifluoromethyl)oxy]benzamide 357.7 136 306 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(3- nitrophenyl)methyl]oxy}benzamide 390.4 137 307 (4R)-2-(4-fluoro-3-prop-2-enylphenyl)-N- hydroxy-4,5-dihydro-1,3-oxazole-4- carboxamide 265.3 138 308 3-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (methyloxy)benzamide 287.3 139 309 4-(but-3-enyloxy)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 309.3 140 310 3-bromo-5-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(prop-2- enyloxy)benzamide 392.2 141 311 4-fluoro-N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-prop-2- enylbenzamide 297.3 142 312 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (prop-2-enyloxy)-3-(trifluoromethyl) benzamide 363.3 143 313 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (methyloxy)benzamide 269.3 144 314 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3- (phenyloxy)benzamide 331.3 145 315 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (methyloxy)-3- [(trifluoromethyl)oxy]benzamide 353.3 146 316 N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(trifluoromethyl)oxy]benzamide 323.2 147 317 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(trifluoromethyl)oxy]benzamide 323.2 148 318 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (trifluoromethyl)benzamide 307.2 149 319 3,4-difluoro-N-{(2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 275.2 150 320 N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (methyloxy)benzamide 269.3 151 321 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}- 4′-propyl-1,1′-biphenyl-4- carboxamide 357.4 152 322 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}- 4′-propyl-1,1′-biphenyl-4- carboxamide 357.4 153 323 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}- 4-[trifluoro(methylidene)-lambda˜6˜- sulfanyl]benzamide 341.3 154 324 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 239.2 155 325 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}- 1,1′-biphenyl-4-carboxamide 315.3 156 326 3-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (methyloxy)benzamide 348.2 157 327 4-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3- (prop-2-enyloxy)benzamide 313.3 158 328 2,3,5,6-tetrafluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-prop- 2-enylbenzamide 351.3 159 329 3-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- (trifluoromethyl)benzamide 325.2 160 330 4-bromo-2-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 336.1 161 331 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (phenyloxy)benzamide 331.3 162 332 4-(dimethylamino)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 282.3 163 333 2-[3-fluoro-4-(methyloxy)-5-prop-2- enylphenyl]-N-hydroxy-4,5-dihydro-1,3- oxazole-4-carboxamide 295.3 164 334 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- [3-(trifluoromethyl)phenyl]furan-2-carboxamide 373.3 165 335 4-{[(1E)-1,2-difluorobuta-1,3-dienyl]oxy}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 343.3 166 336 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}quinoline- 2-carboxamide 290.3 167 337 N-[2-(hydroxyamino)-1-(hydroxymethyl)-2- oxoethyl]-1,1′-biphenyl-4-carboxamide 301.3 168 338 N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1- biphenyl-4-carboxamide 315.3 169 339 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2′- methyl-1,1′-biphenyl-4-carboxamide 329.4 170 340 N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (trifluoromethyl)benzamide 307.2 171 341 4-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3- (trifluoromethyl)benzamide 325.2 172 342 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[(3- nitrophenyl)oxy]methyl}benzamide 390.4 173 343 N-[(1R)-2-(hydroxyamino)-1- (mercaptomethyl)-2-oxoethyl]-4- [(trifluoromethyl)oxy]benzamide 325.3 174 344 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,3- benzodioxole-5-carboxamide 283.3 175 345 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6- (trifluoromethyl)pyridine-3-carboxamide 308.2 176 346 N-{3-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(trifluoromethyl)oxy]benzamide 323.2 177 347 N-{3-hydroxy-1- [(hydroxyamino)carbonyl]propyl}- 1,1′-biphenyl-4-carboxamide 315.3 178 348 N-{(1S,2R)-2-hydroxy-1- (hydroxyamino)carbonyl]propyl}-4- [hydroxy(phenyl)methyl]benzamide 345.4 179 349 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[({4- [(trifluoromethyl)oxy]phenyl}oxy) methyl]benzamide 429.4 180 350 4-[({4-bromo-2-[(trifluoromethyl) oxy]phenyl}oxy)methyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 508.3 181 351 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3′- nitro-1,1′-biphenyl-4-carboxamide 360.3 182 352 4-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 318.1 183 353 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- (methyloxy)-1,1′-biphenyl-4-carboxamide 345.4 184 354 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- [(trifluoromethyl)oxy]-1,1′-biphenyl-4- carboxamide 399.3 185 355 4′-(ethyloxy)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 359.4 186 356 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{5-[(Z)- (hydroxyimino)methyl]thien-2-yl}benzamide 364.4 187 357 3′-(ethyloxy)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 359.4 188 358 (2R,3R)-N,3-dihydroxy-1-({4- [(trifluoromethyl)oxy]phenyl}carbonyl) pyrrolidine-2-carboxamide 335.2 189 359 N-[2-(hydroxyamino)-1-(hydroxymethyl)-2- oxoethyl]-3-(1-methylethyl)-4- (methyloxy)benzamide 297.3 190 360 N-[2-(hydroxyamino)-1-(hydroxymethyl)-2- oxoethyl]-3-(1-methylethyl)-4-(prop-2- enyloxy)benzamide 323.4 191 361 N-[2-(hydroxyamino)-1-(hydroxymethyl)-2- oxoethyl]-4-(methyloxy)-3-propylbenzamide 297.3 192 362 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- (methylthio)-1,1′-biphenyl-4-carboxamide 361.4 193 363 5-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}thiophene-2-carboxamide 324.2 194 364 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-{4- [(trifluoromethyl)oxy]phenyl}thiophene- 2-carboxamide 405.4 195 365 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1- benzofuran-2-carboxamide 279.3 196 366 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- phenylthiophene-2-carboxamide 321.4 197 367 4′-(dimethylamino)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 358.4 198 368 (2S,3R)-N,3-dihydroxy-2-[({2- [(trifluoromethyl)oxy]phenyl}acetyl) amino]butanamide 337.3 199 369 5-[4-(ethyloxy)phenyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}thiophene-2-carboxamide 365.4 200 370 5-[3-(ethyloxy)phenyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}thiophene-2-carboxamide 365.4 201 371 (4R)-N-hydroxy-2-{2′-[(trifluoromethyl)oxy]- 1,1′-biphenyl-4-yl}-4,5-dihydro-1,3- oxazole-4-carboxamide 367.3 202 372 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- (hydroxymethyl)-1,1′-biphenyl-4- carboxamide 345.4 203 373 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {5-[(4-methylpiperazin- 1-yl)methyl]thien-2- yl}benzamide 433.5 204 374 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- (methyloxy)phenyl]carbonyl}benzamide 373.4 205 375 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(E)- phenyldiazenyl]benzamide 343.4 206 376 (4R)-N-hydroxy-2-{4-(methyloxy)-3- [(trifluoromethyl)oxy]phenyl}-4,5- dihydro-1,3-oxazole-4-carboxamide 321.2 207 377 4′-ethyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 343.4 208 378 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- (trifluoromethyl)-1,1′-biphenyl-4- carboxamide 383.3 209 379 5-(4-ethylphenyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}thiophene- 2-carboxamide 349.4 210 380 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-[4- (methylthio)phenyl]thiophene-2-carboxamide 351.4 211 381 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-[4- (methylthio)phenyl]thiophene-2-carboxamide 367.5 212 382 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-(3- nitrophenyl)thiophene-2-carboxamide 366.4 213 383 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-oxo- 4H-chromene-2-carboxamide 307.3 214 384 N-[1-[(hydroxyamino)carbonyl]-1- (hydroxymethyl)-2-methylpropyl]-4- [(trifluoromethyl)oxy]benzamide 351.3 215 385 N-[2-hydroxy-3-(hydroxyamino)-3-oxopropyl]- 1,1′-biphenyl-4-carboxamide 301.3 216 386 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(E)-2- phenylethenyl]benzamide 341.4 217 387 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-9H- fluorene-2-carboxamide 327.4 218 388 4′-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]-1,1′-biphenyl-4-carboxylic acid 359.3 219 389 N-[2-(hydroxyamino)-1-(hydroxymethyl)-2- oxoethyl]-4-(prop-2-enyloxy)-3- propylbenzamide 323.4 220 390 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- iodobenzamide 365.1 221 391 4′-hydroxy-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 331.3 222 392 6-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}pyridine-2- carboxamide 319.1 223 393 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6- phenylpyridine-2-carboxamide 316.3 224 394 4′-butyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 371.4 225 395 4′-(1,1-dimethylethyl)-N-{(1S,2R)-2-hydroxy- 1-[(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 371.4 226 396 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5-[3- (methyloxy)phenyl]thiophene-2-carboxamide 351.4 227 397 4′-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl-1,1′-biphenyl-4-yl dihydrogen phosphate 411.3 228 398 N-ethyl-N′-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4,4′-dicarboxamide 386.4 229 399 N-[(1S,2R)-1-(hydrazmocarbonyl)-2- hydroxypropyl]-4′-propyl-1,1′-biphenyl-4- carboxamide 356.4 230 400 N-{(1S,2R)-2-hydroxy-1- [(methylamino)carbonyl]propyl}-4′- propyl-1,1′-biphenyl-4-carboxamide 355.4 231 401 N-[(1S,2R)-1-(hydrazinocarbonyl)-2- hydroxypropyl]-4-(methyloxy)benzamide 268.3 232 402 (2S,3R)-2-[(1,1′-biphcnyl-4-ylsulfonyl)amino]- N,3-dihydroxybutanamide 351.4 233 403 4-hydroxy-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 255.2 234 404 3′-cyano-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 340.3 235 405 1-dimethylethyl ({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}oxy)acetate 369.4 236 406 (2S,3R)-2-[(1,1′-biphenyl-4- ylsulfonyl)(methyl)amino]-N,3- dihydroxybutanamide 365.4 237 407 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3′-[(Z)- (hydroxyimino)methyl]-4′-(methyloxy)-1,1′- biphenyl-4-carboxamide 388.4 238 408 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(phenylcarbonyl)amino]benzamide 358.4 239 409 N-hydroxy-2-[3-(1-methylethyl)-4-(prop-2- enyloxy)phenyl]-4,5-dihydro-1,3-oxazole-4- carboxamide 305.3 240 410 4′-butyl-N-{(1S,2R)-2-hydroxy-1- [(methylamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 369.5 241 411 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(5- methylpyridin-2-yl)benzamide 330.4 242 412 5-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}pyridine- 3-carboxamide 319.1 243 413 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- pyridin-3-ylbenzamide 316.3 244 414 N-{(1R,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-N′- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4,4′-dicarboxamide 475.5 245 415 (2S,3R)-N,3-dihydroxy-2-[({4-[(E)-2- phenylethenyl]phenyl}methyl) amino]butanamide 327.4 246 416 4-{[(4-bromophenyl)sulfonyl]amino}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 473.3 247 417 1,1-dimethylethyl-4-({4-[({(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}amino)-4- oxobutylcarbamate 439.5 248 418 4-[(4-amniobutanoyl)amino]-N-{(1S,2R)- 2-hyroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 339.4 249 419 1,1-dimethylethyl {4′-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) methyl]-1,1′-biphenyl-4-yl}methylcarbamate 430.5 250 420 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- pyrimidin-5-ylbenzamide 317.3 251 421 1,1-dimethylethyl 5-{4-[({(1S,2R)-2-hydroxy- 1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}pyridine- 3-carboxylate 416.4 252 422 5-{4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}pyridine-3- carboxylic acid 360.3 253 423 (4S)-N-hydroxy-2-{4-(methyloxy)-3- [(trifluoromethyl)oxy]phenyl}-4,5-dihydro- 1,3-oxazole-4-carboxamide 321.2 254 424 (2S,3R)-2-({[4′-(aminomethyl)-1,1′-biphenyl-4- yl]methyl}amino)-N,3-dihydroxybutanamide 330.4 255 425 (3S)-1-hydroxy-3-[(1R)-1-bydroxyethyl]- 4-({4-[(E)-2-phenylethenyl]phenyl}methyl)piperazine-2,6-dione 367.4 256 426 (2S,3R)-N,3-dihydroxy-2-({[4- (phenylethynyl)phenyl]methyl}amino) butanamide 325.4 257 427 N-(3-aminopropyl)-N′-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzene-1,4-dicarboxamide 339.4 258 428 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (propanoylamino)benzamide 310.3 259 429 1,1-dimethylethyl 3-[({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}carbonyl)amino]propylcarbamate 439.5 260 430 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- (phenyloxy)-1,1′-biphenyl-4-carboxamide 407.4 261 431 N-[(1S,2R)-1-({[cyano(phenyl)methyl]amino}carbonyl)-2-hydroxypropyl]- 4′-hydroxy-1,1′-biphenyl-4- carboxamide 430.5 262 432 4′-{[2-(hydroxyamino)-2-oxoethyl]oxy}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 404.4 263 433 4-({[(1S,2R)-1- {[(cyanomethyl)amino]carbonyl}-2- (propanoyloxy)propyl]amino}carbonyl)-1,1′- biphenyl-4-yl propanoate 466.5 264 434 4′-({[(1S,2R)-1- {[(cyanomethyl)(propanoyl)amino]carbonyl}- 2-(propanoyloxy)propyl]amino}carbonyl)- 1,1′-biphenyl-4-yl propanoate 522.6 265 435 N-((1S,2R)-1- {[(cyanomethyl)amino]carbonyl}-2- hydroxypropyl)-4′-hydroxy-1,1′-biphenyl-4- carboxamide 354.4 266 436 (2S,3S)-2-[(1,1′-biphenyl-4-ylnethyl)amino]- N,3-dihydroxybutanamide 301.4 267 437 N-{2-hydroxy-1-[(hydroxyamino)carbonyl]-2- phenylethyl}-1,1′-biphenyl-4-carboxamide 377.4 268 438 (2S,3R)-2-[(diphenylacetyl)amino]-N,3- dihydroxybutanamide 329.4 269 439 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-6- [(phenylmethyl)thio]pyridine-3-carboxamide 362.4 270 440 N,3-dihydroxy-2-({[4- (phenyloxy)phenyl]methyl}amino)butanamide 317.4 271 441 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2′- [(trifluoromethyl)oxy]-1,1′-biphenyl-4- carboxamide 399.3 272 442 (2R,3S)-2-[(1,1′-biphenyl-4-ylmethyl)amino]- N,3-dihydroxybutanamide 301.4 273 443 4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]benzoic acid 283.3 274 444 1,1-dimethylethyl 4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]benzoate 339.4 275 445 (4R)-4-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-5-(hydroxyamino)-5- oxopentanoic acid 371.4 276 446 4′-ethyl-N-[(1R)-2-(hydroxyamino)-1- (hydroxymethyl)-2-oxoethyl]-1,1′-biphenyl- 4-carboxamide 329.4 277 447 4′-ethyl-N-[(1S)-2-(hydroxyamino)-1- (hydroxymethyl)-2-oxoethyl]-1,1′-biphenyl- 4-carboxamide 329.4 278 448 (2S)-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]- N,4-dihydroxypyrrolidine-2-carboxamide 355.4 279 449 4′-ethyl-N-{(1S)-1- [(hydroxyamino)carbonyl]but-3-ynyl}-1,1′- biphenyl-4-carboxamide 337.4 280 450 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4′-ethyl-1,1′-biphenyl-4- carboxamide 328.4 281 451 N-{(1S)-1-[(hydroxyamino)carbonyl]-2- methylpropyl}-1,1′-biphenyl-4-carboxamide 313.4 282 452 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-N-methyl- 1,1′-biphenyl-4-carboxamide 329.4 283 453 4-ethynyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 263.3 284 454 4-(1,3-benzodioxol-5-yl)-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 359.3 285 455 N-{(1R,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′-propyl- 1,1′-biphenyl-4-carboxamide 357.4 286 456 2-({[3′-(ethyloxy)-1,1′-biphenyl-4- yl]methyl}amino)-N,3-dihydroxybutanamide 345.4 287 457 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3′,4′- bis(methyloxy)-1,1′-biphenyl-4-carboxamide 375.4 288 458 3′-formyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- (methyloxy)-1,1′-biphenyl-4-carboxamide 373.4 289 459 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4- [({(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}buta-1,3-diynyl)benzamide 523.5 290 460 (2S,3R)-2-({[4′-(ethyloxy)-1,1′-biphenyl-4- yl]methyl}amino)-N,3-dihydroxybutanamide 345.4 291 461 3′-chloro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (methyloxy)-1,1′-biphenyl-4-carboxamide 379.8 292 462 (1R,2R)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2- phenylcyclopropanecarboxamide 279.3 293 463 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(1H- pyrrol-1-yl)benzamide 304.3 294 464 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- propylbenzamide 281.3 295 465 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- pentylbenzamide 309.4 296 466 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- octylbenzamide 351.5 297 467 (2E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-(4- methylphenyl)prop-2-enamide 279.3 298 468 (2E)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3-[4- (trifluoromethyl)phenyl]prop-2-enamide 333.3 299 469 (2E)-3-(1,1′-biphenyl-4-yl)-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}prop-2- enamide 341.4 300 470 (2S,3R)-2-[(1,1′-biphenyl-4-ylacetyl)amino]- N,3-dihydroxybutanamide 329.4 301 471 (2S,3R)-2-{[(2S)-2-amino-3-(1,1′-biphenyl-4- yl)propanoyl]amino}-N,3- dihydroxybutanamide 358.4 302 472 (2S,3R)-2-{[(2R)-2-amino-3-(1,1′-biphenyl-4- yl)propanoyl]amino}-N,3- dihydroxybutanamide 358.4 303 473 (3S)-3-amino-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-5- phenylpentanamide 310.4 304 474 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(phenylamino)methyl]benzamide 344.4 305 475 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[(phenylmethyl)amino]methyl}benzamide 358.4 306 476 4′-ethyl-N-{(1S,2R)-2-hydroxy-1- [({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 444.5 307 477 (2S,3R)-2-[(1,1-biphenyl-4-ylacetyl)amino]-3- hydroxy-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}butanamide 430.5 308 478 4-(4-chlorophenyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}cyclohexane carboxamide 355.8 309 479 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(1H- pyrazol-1-yl)benzamide 305.3 310 480 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- morpholin-4-ylbenzamide 324.3 311 481 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(1,2,3- thiadiazol-4-yl)benzamide 323.3 312 482 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- methylpiperazin-1-yl)methyl]benzamide 351.4 313 483 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(1H- imidazol-1-ylmethyl)benzamide 319.3 314 484 (2S,4S)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- phenylpyrrolidine-2-carboxamide 308.3 315 485 4′-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 394.2 316 486 4′-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 394.2 317 487 4′-bromo-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 394.2 318 488 (2R)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-N˜1˜- hydroxypentanediamide 370.4 319 489 (2S,3S)-1-[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]-3-hydroxypyrrolidine-2- carboxylic acid 340.4 320 490 (2S,3S)-N-[(1,1-dimethylethyl)oxy]-1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]-3- hydroxypyrrolidine-2-carboxamide 411.5 321 491 (2S,3S)-1-[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]-N,3-dihydroxypyrrolidine-2- carboxamide 355.4 322 492 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-nitrophenyl)ethynyl]benzamide 384.4 323 493 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]prapyl}-4- {[4-(1H-pyrrol-1-yl)phenyl]ethynyl}benzamide 404.4 324 494 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4′- nitro-1,1′-biphenyl-4-carboxamide 360.3 325 495 (2S,3R)-N,3-dihydroxy-2-({[4′-(methyloxy)-3′- propyl-1,1′-biphenyl-4- yl]methyl}amino)butanamide 373.5 326 496 4′-cyano-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 340.3 327 497 (2S,3R)-2-({[4-(ethyloxy)-4-(methyloxy)-1,1′- biphenyl-3-yl]methyl}amino)-N,3- dihydroxybutanamide 375.4 328 498 2′,5′-difluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 351.3 329 499 N-[(1S)-1-[(acetylamino)methyl]-2- (hydroxyamino)-2-oxoethyl]4-ethyl-1,1′- biphenyl-4-carboxamide 370.4 330 500 N-{(1S)-4-amino-1- [(hydroxyamino)carbonyl]butyl}4-ethyl-1,1′- biphenyl-4-carboxamide 356.4 331 501 4′-ethyl-N-[(1S)-2-(hydroxyamino)-1-(1H- imidazol-5-ylmethyl)-2-oxoethyl]-1,1′- biphenyl-4-carboxamide 379.4 332 502 (2S,3R)-2-{[1-(1,1′-biphenyl-4- yl)ethyl]amino}-N,3-dihydroxybutanamide 315.4 333 503 (2S,3R)-2-{[1-(1,1′-biphenyl-4- yl)propyl]amino}-N,3-dihydroxybutanamide 329.4 334 504 (2S,3R)-2-{[1-(4′-bromo-1,1′-biphenyl-4- yl)ethyl]amino}-N,3-dihydroxybutanamide 394.3 335 505 (2S,3R)-N,3-dihydroxy-2-{[1-(4′-methyl-1,1′- biphenyl-4-yl)ethyl]amino}butanamide 329.4 336 506 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-1,1′-biphenyl-4-carboxamide 300.3 337 507 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(1H-pyrrol-1-yl)benzamide 289.3 338 508 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4- chlorophenyl)cyclohexanecarboxamide 340.8 339 509 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-pentylbenzamide 294.4 340 510 (2E)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-3-(1,1′-biphenyl- 4-yl)prop-2-enamide 326.4 341 511 (2S)-3-amino-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)methyl]amino}-N-hydroxypropanamide 314.4 342 512 (2S)-3-amino-2-[(1,1′-biphenyl-4- ylmethyl)amino]-N-hydroxypropanamide 286.3 343 513 (2S)-3-amino-2-{[1-(4′-bromo-1,1′-biphenyl-4- yl)ethyl]amino}-N-hydroxypropanamide 379.3 344 514 (2S)-3-amino-N-hydroxy-2-{[1-(4′-methyl-1,1′- biphenyl-4-yl)ethyl]amino}propanamide 314.4 345 515 4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-1- (hydroxymethyl)-2-oxoethyl]-1,1′-biphenyl- 4-carboxamide 430.5 346 516 4′-ethyl-N-{(1S)-2-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-1-[(4- hydroxyphenyl)methyl]-2-oxoethyl}-1,1′- biphenyl-4-carboxamide 506.6 347 517 (2S)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-N˜1˜-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino)carbonyl]propyl}pentanediamide 471.5 348 518 (4S)-4-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-5-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)- 5-oxopentanoic acid 472.5 349 519 (3S)-3-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-4-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-4- oxobutanoic acid 458.5 350 520 (3S)-2-(1,1′-biphenyl-4-ylacetyl)-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}-1,2,3,4- tetrahydroisoquinoline-3-carboxamide 488.6 351 521 4′-ethyl-N-[(1S)-2-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-1- methyl-2-oxoethyl]-1,1′-biphenyl-4- carboxamide 414.5 352 522 (2S,3R)-2-({(2S)-3-amino-2-[(1,1′-biphenyl-4- ylacetyl)amino]propanoyl}amino)-N,3- dihydroxybutanamide 415.5 353 523 (2S)-2-[(1,1′-biphenyl-4-ylacetyl)amino]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}pent-4-ynamide 424.5 354 524 (2S,3R)-2-{[(2S)-2-amino-2-(1,1′-biphenyl-4- yl)ethanoyl]amino}-N,3-dihydroxybutanamide 344.4 355 525 (2S,3R)-2-{[(2R)-2-amino-2-(1,1′-biphenyl-4- yl)ethanoyl]amino}-N,3-dihydroxybutanamide 344.4 356 526 N-(3-aminopropyl)-4′-ethyl-N-[2- (hydroxyamino)-2-oxoethyl]-1,1′-biphenyl-4- carboxamide 356.4 357 527 N-(2-cyanoethyl)-4′-ethyl-N-[2- (hydroxyamino)-2-oxoethyl]-1,1′- biphenyl-4-carboxamide 352.4 358 528 N-[2-(acetylamino)ethyl]4-ethyl-N-[2- (hydroxyamino)-2-oxoethyl]-1,1′-biphenyl-4- carboxamide 384.4 359 529 4′-ethyl-N-[2-(hydroxyamino)-2-oxoethyl]-N- prop-2-ynyl-1,1′-biphenyl-4-carboxamide 337.4 360 530 4-cyano-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 264.3 361 531 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-cyanobenzamide 249.2 362 532 1,1-dimethylethyl (2S)-2-{[(4- ethynylphenyl)carbonyl]amino}-3- (hydroxyamino)-3-oxopropylcarbamate 348.4 363 533 1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-[({4-[(E)-2-phenylethenyl]phenyl}methyl)amino]propylcarbamate 412.5 364 534 N-{(1R,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3′- (trifluoromethyl)-1,1′-biphenyl-4-carboxamide 383.3 365 535 (2S,3R)-2-[(1,1′-biphenyl-4-ylmethyl)amino]- 3-hydroxybutanoic acid 286.3 366 536 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-(phenylethynyl)benzamide 324.4 367 537 1,1-dimethylethyl (2S)-3-(hydroxyamino)- 3-oxo-2-({[4-(phenylethynyl) phenyl]carbonyl}amino)propyl carbamate 424.5 368 538 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-ethynylbenzamide 248.3 369 539 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-ethynylbenzamide 248.3 370 540 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-(methyloxy)phenyl]ethynyl}benzamide 369.4 371 541 (2S)-3-amino-N-hydroxy-2-[({4-[(E)-2- phenylethenyl]phenyl}methyl)amino]propanamide 312.4 372 542 1,1-dimethylethyl 2-{4′-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]- 1,1′-biphenyl-4-yl}ethylcarbamate 458.5 373 543 (2S,3R)-N,3-dihydroxy-2-[({4′-[(2-pyrrolidin- 1-ylethyl)oxy]-1,1′-biphenyl-4- yl}methyl)amino]butanamide 414.5 374 544 1,1-dimethylethyl (1S)-4-({[(1,1- dimethylethyl)oxy]carbonyl}amino)-1- ({[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}ethynyl)phenyl]amino}carbonyl)butylcarbamate 668.8 375 545 4-(4-chlorophenyl)-N-[(1S)-2-({(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}amino)-1-methyl-2- oxoethyl]cyclohexanecarboxamide 426.9 376 546 4′-ethyl-N-[2-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-2- oxoethyl]-1,1′-biphenyl-4-carboxamide 400.4 377 547 4′-ethyl-N-[3-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-3- oxopropyl]-1,1′-biphenyl-4-carboxamide 414.5 378 548 4′-ethyl-N-[4-({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)-4- oxobutyl]-1,1′-biphenyl-4-carboxamide 428.5 379 549 N-((1S)-2-{[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}-1-methyl- 2-oxoethyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 399.5 380 550 N-(2-{[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}-2- oxoethyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 385.4 381 551 N-(3-{[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}-3- oxopropyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 399.5 382 552 N-(4-{[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}-4- oxobutyl)-4′-ethyl-1,1′-biphenyl-4- carboxamide 413.5 383 553 4′-ethyl-N-[1-[(hydroxyamino)carbonyl]-2- (methyloxy)propyl]-1,1′-biphenyl-4- carboxamide 357.4 384 554 4-ethyl-N-[(1S,2R)-1- [(hydroxyamino)carbonyl]-2- (methyloxy)propyl]-1,1′-biphenyl-4- carboxamide 357.4 385 555 N-[1-[(dimethylamino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 356.4 386 556 N-{(1S)-3-cyano-1- [(hydroxyamino)carbonyl]propyl}-4′-ethyl- 1,1′-biphenyl-4-carboxamide 352.4 387 557 N-{(1S)-5-amino-1- [(hydroxyamino)carbonyl]pentyl}-4′-ethyl- 1,1′-biphenyl-4-carboxamide 370.5 388 558 N-{(1S)-3-amino-1- [(hydroxyamino)carbonyl]propyl}-4′-ethyl- 1,1′-biphenyl-4-carboxamide 342.4 389 559 4′-ethyl-N-hydroxy-1,1′-biphenyl-4- carboxamide 242.3 390 560 4′-ethyl-N-{2-hydroxy-1- [(hydroxyamino)carbonyl]-2-methylpropyl}- 1,1′-biphenyl-4-carboxamide 357.4 391 561 N-[(2S)-2-{[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-3-(hydroxyamino)-3- oxopropyl]morpholine-4-carboxamide 441.5 392 562 N-[(1S)-1-{[(aminocarbonyl)amino]methyl}-2- (hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 371.4 393 563 N-[(1S)-1- ({[amino(imino)methyl]amino}methyl)-2- (hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 370.4 394 564 N-[(2S)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4′-ethyl-1,1′-biphenyl-4- carboxamide 328.4 395 565 1-[(4′-ethyl-1,1′-biphenyl-4-yl)carbonyl]-N- hydroxypiperazine-2-carboxamide 354.4 396 566 N-[(2S)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4-(phenylethynyl)benzamide 324.4 397 567 N-hydroxy-1-{[4-(phenylethynyl) phenyl]carbonyl}piperazine-2- carboxamide 350.4 398 568 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- pentylphenyl)ethynyl]benzamide 409.5 399 569 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[3- (methyloxy)phenyl]ethynyl}benzamide 369.4 400 570 4-[(3-fluoro-4-methylphenyl)ethynyl]-N- {(1S,2R)-2-hydxoxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 371.4 401 571 4-[(2,4-difluorophenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 375.3 402 572 methyl (2E)-3-(ethylamino)-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)but-2-enoate 363.4 403 573 1,1-dimethylethyl 4-{[(2S)-3-(hydroxyamino)- 3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]amino}- 4-oxobutylcarbamate 509.6 404 574 N-(1-(N-hydroxycarbamoyl)-2-hydroxy-3- methylbutyl)[4-(4- ethylphenyl)phenyl]carboxamide 371.4 405 575 N-((1R,2R)-1-{[(aminocarbonyl) (hydroxy)amino]methyl}-2- hydroxypropyl)-4′-ethyl-1,1′- biphenyl-4-carboxamide 372.4 406 576 4′-ethyl-N-((1R,2R)-1- {[formyl(hydroxy)amino]methyl}-2- hydroxypropyl)-1,1′-biphenyl-4-carboxamide 357.4 407 577 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- (trifluoromethyl)phenyl]ethynyl}benzamide 407.4 408 578 1,1-dimethylethyl 2-{[(2S)-3-(hydroxyamino)- 3-oxo-2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-2-oxoethylcarbamate 481.5 409 579 N-[(1S)-1-{[(aminoacetyl)amino]methyl}-2- (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 381.4 410 580 N-[(1S)-1-{[(4-aminobutanoyl)amino]methyl}- 2-(hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 409.5 411 581 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-pent-1- ynylbenzamide 305.3 412 582 N-{(1S,2R)-2-[(1,1-dimethylethyl)oxy]-1- [(hydroxyamino)carbonyl]propyl}-4′-propyl- 1,1′-biphenyl-4-carboxamide 413.5 413 583 1,1-dimethylethyl (1S)-4-({[(1,1- dimethylethyl)oxy]carbonyl}amino)-1- {[(2-55 4′-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]-1,1′-biphenyl-4- yl}ethyl)amino]carbonyl}butylcarbamate 672.8 414 584 4′-(2-aminoethyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 358.4 415 585 4′-(2-{[(2S)-2,5-diaminopentanoyl]amino}ethyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}- 1,1′-biphenyl-4-carboxamide 472.6 416 586 4-(cyclohex-1-en-1-ylethynyl)-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 343.4 417 587 4-(3,3-dimethylbut-1-ynyl)-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 319.4 418 588 N-{(1S)-1-{[(aminoacetyl)amino]methyl}-2- [(2-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4- (phenylethynyl)phenyl]carbonyl}amino) propyl]amino}-2-oxoethyl)amino]-2- oxoethyl}-4-(phenylethynyl)benzamide 728.8 419 589 4-[(4-{[(2S)-2,5-diaminopentanoyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 468.5 420 590 4′-(2-aminoethyl)-N-{(1E)-1- [(hydroxyamino)carbonyl]prop-1-enyl}- 1,1′-biphenyl-4-carboxamide 340.4 421 591 2′,4′-difluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′- biphenyl-4-carboxamide 351.3 422 592 N-[(1E)-1-formylprop-1-enyl]-4′-propyl-1,1- biphenyl-4-carboxamide 308.4 423 593 N-hydroxy-4-(pyridin-3-ylethynyl)benzamide 239.2 424 594 4-(3-hydroxy-3,5-dimethylhex-1-ynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 363.4 425 595 4′-ethyl-N-{(1R,2R)-2-hydroxy-1- [(hydroxyamino)methyl]propyl}-1,1′- biphenyl-4-carboxamide 329.4 426 596 4′-ethyl-N-{(1R,2R)-1- [(hydroxyamino)methyl]-2- [(phenylmethyl)oxy]propyl}-1,1′- biphenyl-4-carboxamide 419.5 427 597 4′-ethyl-N-[(5R,6R)-3-hydroxy-6-methyl-2- oxo-1,3-oxazman-5-yl]-1,1′-biphenyl-4- carboxamide 355.4 428 598 N-((1R,2R)-1 {[({[2-(dimethylamino) ethyl]amino}carbonyl)(hydroxy) amino]methyl}-2-hydroxypropyl)-4′- ethyl-1,1′-biphenyl-4-carboxamide 443.6 429 599 N-((1R,2R)-1-{[{[(2-cyanoethyl)amino]carbonyl}(hydroxy)amino]methyl}- 2-hydroxypropyl)-4′-ethyl-1,1′- biphenyl-4-carboxamide 425.5 430 600 4′-ethyl-N-((1R,2R)-2-hydroxy-1- {[hydroxy({[3-(2-oxopyrrolidin- 1-yl)propyl]amino}carbonyl)amino]methyl}propyl)-1,1′-biphenyl-4-carboxamide 497.6 431 601 (1R,2R)-3-[({[2-(dimethylamino)ethyl]amino}carbonyl)(hydroxy)amino]-2- {[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-1-methylpropyl 2- (dimethylamino)ethylcarbamate 557.7 432 602 (1R,2R)-3-[{[(2-cyanoethyl)amino]carbonyl}(hydroxy)amino]-2- {[(4′-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-1-methylpropyl 2- cyanoethylcarbamate 521.6 433 603 N-{(1E)-1-[(E)-(hydroxylmino)methyl]prop-1- enyl}-4′-propyl-1,1′-biphenyl-4-carboxamide 323.4 434 604 N-{(1S,2R)-2-hydroxy-1-(hydroxyamino) carbonyl]propyl}-4-(pyridin-3- ylethynyl)benzamide 340.3 435 605 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[3- (methylamino)prop-1-ynyl]benzamide 306.3 436 606 N-[(1S)-1-[(dimethylamino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 356.4 437 607 N-[1-(N-hydroxycarbamoylmethyl)(1R,2R)- 2-hydroxypropyl][4-(4- ethylphenyl)phenyl]carboxamide 357.4 438 608 N-[(1S)-1-[(diethylamino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4′-ethyl-1,1′- biphenyl-4-carboxamide 384.5 439 609 4-[(3-aminophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 354.4 440 610 4-[3-(dimethylamino)prop-1-ynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 320.4 441 611 4-[3-(dimethylamino)prop-1-ynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 320.4 442 612 4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.4 443 613 3′-fluoro-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]-4′-methyl- 1,1′-biphenyl-4-carboxamide 347.4 444 614 N-[(1S)-1-formyl-2-methylpropyl]-1,1′- biphenyl-4-carboxamide 282.4 445 615 N-{(1S)-1-[(E)-(hydroxylmino)methyl]-2- methylpropyl}-1,1′-biphenyl-4-carboxamide 297.4 446 616 N-((1E)-1-{(E)-[(aminocarbonyl) hydrazono]methyl}prop-1- enyl)-4′-propyl-1,1′-biphenyl-4-carboxamide 365.4 447 617 4-[(4-aminophenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 354.4 448 618 4-{[3-(aminomethyl)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 368.4 449 619 N-(2-aminoethyl)-3-({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)benzamide 425.5 450 620 N-((1S)-1-{(1E)-[(aminocarbonyl) hydrazono]methyl}-2- methylpropyl)-1,1′-biphenyl-4-carboxamide 339.4 451 621 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[3- (propanoylamino)phenyl]ethynyl}benzamide 410.4 452 622 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[3- (morpholin-4- ylmethyl)phenyl]ethynyl}benzamide 438.5 453 623 4-[(3-{[(2-aminoethyl)amino]methyl}phenyl) ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.5 454 624 N-[(1R)-2-(hydroxyamino)-1-(hydroxymethyl)- 2-oxoethyl]-4′-propyl-1,1′-biphenyl-4- carboxamide 343.4 455 625 N-[1-(N-hydroxycarbamoylmethyl)(1R,2R)-2- hydroxypropyl][4-(2- phenylethynyl)phenyl]carboxamide 353.4 456 626 4′-ethyl-N-[(1R,2R)-1- [(hydroxyamino)carbonyl]-2- (methyloxy)propyl]-1,1′-biphenyl-4- carboxamide 357.4 457 627 4′-ethyl-N-[(1S)-1-[(ethylamino)methyl]-2- (hydroxyaxnmo)-2-oxoethyl]-1,1′- biphenyl-4-carboxamide 356.4 458 628 4′-ethyl-N-[(1S)-2-(hydroxyamino)-2-oxo-1- ({[(2S)-pyrrolidin-2-ylmethyl]amino}methyl)ethyl]-1,1′-biphenyl-4- carboxamide 411.5 459 629 N-[(1S)-1-[(ethylamino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 352.4 460 630 N-[(1S)-2-(hydroxyamino)-2-oxo-1-({[(2S)- pyrrolidin-2-ylmethyl]amino}methyl) ethyl]-4-(phenylethynyl)benzamide 407.5 461 631 4′-ethyl-N-((1S)-2-(hydroxyamino)-1-{[(1- methylethyl)amino]methyl}-2-oxoethyl)-1,1′- biphenyl-4-carboxamide 370.5 462 632 4′-ethyl-N-[(1S)-2-(hydroxyamino)-1-({[2- (methylamino)ethyl]amino}methyl)-2- oxoethyl]-1,1′-biphenyl-4-carboxamide 385.5 463 633 4′-ethyl-N-((1S)-2-(hydroxyamino)-1-{[(1- methylpiperidin-4-yl)amino]methyl}-2- oxoethyl)-1,1′-biphenyl-4-carboxamide 425.5 464 634 N-((1S)-2-(hydroxyamino)-1-{[(1- methylethyl)amino]methyl}-2-oxoethyl)-4- (phenylethynyl)benzamide 366.4 465 635 N-[(1S)-2-(hydroxyamino)-1-({[2- (methylamino)ethyl]amino}methyl)-2- oxoethyl]-4-(phenylethynyl)benzamide 381.4 466 636 N-((1S)-2-(hydroxyamino)-1-{[(1- methylpiperidin-4-yl)amino]methyl}-2- oxoethyl)-4-(phenylethynyl)benzamide 421.5 467 637 N-[(1S)-1-{[(2-aminoethyl)amino]methyl}-2- (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 367.4 468 638 N-[(1S)-1-{[bis(2-aminoethyl)amino]methyl}- 2-(hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 410.5 469 639 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(morpholin-4- ylacetyl)amino]phenyl}ethynyl)benzamide 481.5 470 640 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- (propanoylamino)phenyl]ethynyl}benzamide 410.4 471 641 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(trifluoromethyl)oxy]phenyl}ethynyl)benzamide 423.4 472 642 1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-{[(4-{[3-(propanoylamino) phenyl]ethynyl}phenyl)carbonyl]amino}propylcarbamate 495.5 473 643 1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-([(4-pent-1-ynylphenyl) carbonyl]amino}propylcarbamate 390.4 474 644 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[3- (propanoylamino)phenyl]ethynyl}benzamide 395.4 475 645 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-pent-1-ynylbenzamide 290.3 476 646 4-(phenyloxy)benzaldehyde thiosemicarbazone 272.3 477 647 4-(phenyloxy)benzaldehyde semicarbazone 256.3 478 648 4 {[3-(trifluoromethyl)phenyl]oxy}benzaldehyde thiosemicarbazone 340.3 479 649 4-[(3,4-difluorophenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 375.5 480 650 4-[(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5- yl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 373.3 481 651 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-(4-phenylbuta-1,3- diynyl)benzamide 348.4 482 652 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4′-propyl-1,1′-biphenyl-4- carboxamide 342.4 483 653 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-1,1′:4′,1″-terphenyl-4-carboxamide 376.4 484 654 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-1,1′:4′,1″- terphenyl-4-carboxamide 391.4 485 655 1,1-dimethylethyl (2S)-2-[({4-[(4-{({[(1,1- dimethylethyl)oxy]carbonyl}amino)acetyl]amino}phenyl)ethynyl]phenyl}carbonyl) amino]-3-(hydroxyamino)- 3-oxopropylcarbamate 596.6 486 656 N-[(1S,2R)-1-(hydrazinocarbonyl)-2- hydroxypropyl]-4-(phenylethynyl) benzamide 338.4 487 657 2-[(2S,3R)-3-hydroxy-2-({[4- (phenylethynyl)phenyl]carbonyl}amino) butanoyl]hydrazinecarboxamide 381.4 488 658 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(2- methylphenyl)ethynyl]benzamide 353.4 489 659 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(3- hydroxyphenyl)ethynyl]benzamide 355.4 490 660 4-({3-[(aminoacetyl)amino]phenyl}ethynyl)- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.4 491 661 4-{[4-({[(cyanomethyl)amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 450.5 492 662 4′-ethyl-N-{(1S)-2-(hydroxyamino)-2-oxo-1- [(tetrahydro-2H-pyran-4- ylamino)methyl]ethyl}-1,1′-biphenyl-4- carboxamide 412.5 493 663 N-{(1S)-2-(hydroxyamino)-2-oxo-1- [(tetrahydro-2H-pyran-4- ylamino)methyl]ethyl}-4- (phenylethynyl)benzamide 408.5 494 664 4-[(4-chlorophenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 373.8 495 665 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- methylphenyl)ethynyl]benzamide 353.4 496 666 4-[(2-fluorophenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 357.4 497 667 4-[(3-fluorophenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 357.4 498 668 4-[(4-fluorophenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 357.4 499 669 4-[(4-{[(cyclopropylamino)acetyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 451.5 500 670 4-({4-[({[2-(dimethylamino)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 482.6 501 671 4-({4-[({[2-(acetylamino)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 496.5 502 672 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[3-(2-oxopyrrolidin-1- yl)propyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 536.6 503 673 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(pyridin-3-ylmethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 502.5 504 674 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(2-pyridin-2-ylethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 516.6 505 675 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(4-methylpiperazin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 494.6 506 676 4-({4-[(1,4′-bipiperidin-1′- ylacetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 562.7 507 677 1-(2-{[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}ethynyl)phenyl]amino}-2-oxoethyl)piperidine- 4-carboxamide 522.6 508 678 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(piperidin-3-ylamino) acetyl]amino}phenyl)ethynyl]benzamide 494.6 509 679 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(piperidin-4-ylamino) acetyl]amino}phenyl)ethynyl]benzamide 494.6 510 680 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(piperidin-2- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 508.6 511 681 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(piperidin-3- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 508.6 512 682 4-[(4-{[(3-aminopyrrolidin-1- yl)acetyl]amino}phenyl)ethynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 480.5 513 683 4-({4-[(azepan-1-ylacetyl) amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 493.6 514 684 N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}-4-{[4-({[(4- morpholin-4-ylphenyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 572.6 515 685 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2-hydroxyethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 440.5 516 686 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(cyclopropylamino) acetyl]amino}phenyl)ethynyl]benzamide 436.5 517 687 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[3-(2- oxopyrrolidin-1-yl)propyl]amino}acetyl)amino]phenyl}ethynyl) benzamide 521.6 518 688 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(4- methylpiperazin-1-yl) acetyl]amino}phenyl)ethynyl]benzamide 479.6 519 689 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(pyridin-3- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 487.5 520 690 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(piperidin-1- ylacetyl)amino]phenyl}ethynyl)benzamide 464.5 521 691 4-{[4-({[(2-hydroxyethyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}benzamide 455.5 522 692 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[2-(methyloxy)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 469.5 523 693 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({methyl[2- (methyloxy)ethyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 483.5 524 694 4-{[4-({[[2-(dimethylamino)ethyl](methyl)amino]acetyl}amino) phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy- 1-[(hydroxyamino)carbonyl]propyl}benzamide 496.6 525 695 4-{[4-({[(3R)-3-(dimethylamino) pyrrolidin-1-yl]acetyl}amino) phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 508.6 526 696 4-{[4-({[(3S)-3-(dimethylamino) pyrrolidin-1-yl]acetyl}amino) phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 508.6 527 697 4-{[4-({[(3R)-3-(acetylamino) pyrrolidin-1-yl]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 522.6 528 698 4-{[4-({[(3S)-3-(acetylamino) pyrrolidin-1-yl]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 522.6 529 699 4-{[4-({[(3R)-1-(azabicyclo [2.2.2]oct-3-ylamino]acetyl}amino) phenyl]ethynyl}-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 520.6 530 700 4-{[4-({[(3S)-1-azabicyclo[2.2.2]oct-3-ylamino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 520.6 531 701 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(2R)-pyrrolidin-2- ylmethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 494.6 532 702 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(2S)-pyrralidin-2- ylmethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 494.6 533 703 4-{[4-({[(3-aminocyclohexyl)amino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 508.6 534 704 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(3-hydroxypipendin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 495.5 535 705 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(3-morpholin-4- ylpropyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 538.6 536 706 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(2-methylpropyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 467.5 537 707 4-[(4-{[(ethylamino)acetyl]amino}phenyl)ethynyl]N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 439.5 538 708 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(piperidin-1-ylacetyl) amino]phenyl}ethynyl)benzamide 479.5 539 709 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(3-hydroxypropyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 469.5 540 710 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[3-(methyloxy)propyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 483.5 541 711 4-{[4-({[(2-cyanoethyl)amino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.5 542 712 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(2-pyrrolidin-1-ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 508.6 543 713 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(2-methyl-1H-imidazol-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 476.5 544 714 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- {[(methylamino)acetyl]amino}phenyl) ethynyl]benzamide 410.4 545 715 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2-methylpropyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 452.5 546 716 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[2-(methyloxy) ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 454.5 547 717 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({methyl[2- (methyloxy)ethyl]amino}acetyl) amino)phenyl}ethynyl)benzamide 468.5 548 718 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(3- hydroxypropyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 454.5 549 719 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[3- (methyloxy)propyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 468.5 550 720 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[2- (dimethylamino)ethyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 467.5 551 721 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[[2- (dimethylamino)ethyl](methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 481.6 552 722 4-({4-[({[2-(acetylamino)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N- [(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 481.5 553 723 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2- cyanoethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 449.5 554 724 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2- pyrrolidin-1-ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 493.6 555 725 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[4- (dimethylamino)butyl]amino}acetyl) amino]phenyl}ethynyl) benzamide 495.6 556 726 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(morpholin-4- ylacetyl)amino]phenyl}ethynyl)benzamide 466.5 557 727 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxaethyl]-4-({4-[(azepan-1- ylacetyl)amino]phenyl}ethynyl)benzamide 478.6 558 728 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(pyrrolidin-1- ylacetyl)amino]phenyl}ethynyl)benzamide 450.5 559 729 1-{2-[(4-{[4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl) amino]-2-axoethyl}piperidine-4- carboxamide 507.6 560 730 4-{[4-({[(3R)-3-(acetylamino)pyrrolidin-1- yl]acetyl}amino)phenyl]ethynyl}-N-[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxaethyl]benzamide 507.6 561 731 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(3R)-3- (dimethylamino)pyrrolidin-1- yl]acetyl}amino)phenyl]ethynyl}benzamide 493.6 562 732 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(3-aminopyrrolidin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 465.5 563 733 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(piperidin-3- ylamino)acetyl]amino}phenyl) ethynyl]benzamide 479.6 564 734 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(piperidin- 4-ylamino)acetyl]amino}phenyl) ethynyl]benzamide 479.6 565 735 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(piperidin- 2-ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 493.6 566 736 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(piperidin- 3-ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 493.6 567 737 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(pyridin-2- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 487.5 568 738 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(pyridin-4- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 487.5 569 739 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2-pyridin-2- ylethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 501.6 570 740 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2-pyridin-3- ylethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 501.6 571 741 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2-pyridin-4- ylethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 501.6 572 742 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(phenylamino) acetyl]amino}phenyl)ethynyl]benzamide 472.5 573 743 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(phenylmethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 486.5 574 744 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2- phenylethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 500.6 575 745 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(1H-imidazol-1- ylacetyl)amino]phenyl}ethynyl)benzamide 447.5 576 746 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[(1H-imidazol-1-ylacetyl) amino]phenyl}ethynyl)benzamide 462.5 577 747 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(phenylamino)acetyl]amino}phenyl)ethynyl]benzamide 487.5 578 748 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(2-phenylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 515.6 579 749 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(3-phenylpropyl)amino]acetyl}amino)phenyl]ethnyl}benzamide 529.6 580 750 4-[(3-{[(aminoacetyl)amino]methyl }phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 425.5 581 751 4-[(2-aminopyrimidin-5-yl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 356.4 582 752 4-[(4-acetylphenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 381.4 583 753 N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}-4-[(4-{[({2-[4- (phenylmethyl)piperazin-1-yl]ethyl}amino)acet-yl]amino}phenyl)ethynyl]benzamide 613.7 584 754 4-{[4-({[(aminoacetyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 468.5 585 755 4-{[4-({[4-(2-hydroxyethyl)piperazin-1- yl]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 524.6 586 756 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({(3R)-3-[(trifluoroacetyl)amino]pyrrolidin-1- yl}acetyl)amino]phenyl}ethynyl)benzamide 576.5 587 757 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(methylamino)acetyl]amino}phenyl) ethynyl]benzamide 425.5 588 758 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(piperazin-1-ylacetyl)amino]phenyl}ethynyl)benzamide 480.5 589 759 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[(pyridin-2-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 502.5 590 760 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[(pyridin-4-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 502.5 591 761 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[(2-pyridin-3-ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 516.6 592 762 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[(2-pyridin-4-ylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 516.6 593 763 4-({4-[({[(2-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 519.5 594 764 4-({4-[({[(2-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 536.0 595 765 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[({[2-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl) ethynyl]benzamide 531.6 596 766 4-({4-[({[(3-fluorophenyl)methyl]amino }acetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 519.5 597 767 4-({4-[({[(3-chlorophenyl)methyl]amino }acetyl)amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 536.0 598 768 N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}-4-[(4-{[({[3- (methyloxy)phenyl]methyl}amino) acetyl]amino}phenyl) ethynyl]benzamide 531.6 599 769 N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}-4-({4-[({[(3- methylphenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 515.6 600 770 N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}-4-[(4-{[({[3- (trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl) ethynyl]benzamide 569.5 601 771 N-{(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}-4-([4-({[({3- [(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 585.5 602 772 4-({4-[({[(4-fluorophenyl)methyl]amino}acetyl)′amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy- 1-[(hydroxyamino)carbonyl]propyl}benzamide 519.5 603 773 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 515.6 604 774 4-[(4-{[({[4-(dimethylamino)phenyl]methyl}amino)acetyl]amino}phenyl) ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 544.6 605 775 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[({[4-(trifluoromethyl) phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 569.5 606 776 4-[(4-{[({[4-fluoro-2- (trifluoromethyl)phenyl]methyl}amino) acetyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 587.5 607 777 4-({4-[({[(2,4-difluorophenyl) methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 537.5 608 778 4-({4-[({[(2,4-dichlorophenyl) methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 570.4 609 779 4-{[4-({[(2-fluorophenyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 505.5 610 780 4-{[4-({[(4-fluorophenyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 505.5 611 781 4-({4-[({[(3,5-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl) -N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 537.5 612 782 4-{[4-({[(4-bromophenyl)amino]acetyl}amino)phenyl]ethnyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 566.4 613 783 4-({4-[({[4-(dimethylamino)phenyl]amino}acetyl)amino[phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 530.6 614 784 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(2S)-2- aminopropanoyl]amino}phenyl) ethynyl]benzamide 410.4 615 785 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(2R)-2- aminopropanoyl]amino}phenyl) ethynyl]benzamide 410.4 616 786 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(2S)-2- amino-4-methylpentanoyl]amino}phenyl)ethynyl]benzamide 452.5 617 787 4-[(4-{[(2S,3R)-2-amino-3- hydroxybutanoyl]amino}phenyl)ethynyl- N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 440.5 618 788 4-[(4-{[(2S)-2-amino-4- cyanobutanoyl]amino}phenyl)ethynyl]-N- [(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]benzamide 449.5 619 789 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-diaminopropanoyl]amino}phenyl) ethynyl]benzamide 425.5 620 790 (2S)-N-(4-{[4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl) pyrrolidine-2-carboxamide 436.5 621 791 (2S)-N-(4-{[4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl) pipendine-2-carboxamide 450.5 622 792 N-(4-{[4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl) piperidine-3-carboxamide 450.5 623 793 4-[(4-{[(2S)-2-amino-3-(1H-imidazol-4- yl)propanoyl]amino}phenyl)ethynyl]- N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 476.5 624 794 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- methylphenyl)ethynyl]benzamide 338.4 625 795 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(2- fluorophenyl)ethynyl]benzamide 342.3 626 796 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(3- fluorophenyl)ethynyl]benzamide 342.3 627 797 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- fluorophenyl)ethynyl]benzamide 342.3 628 798 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- chlorophenyl)ethynyl]benzamide 358.8 629 799 4-[(4-{[(2S)-2-amino-4- methylpentanoyl]amino}phenyl)ethynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 467.5 630 800 4-[(4-{[(2S)-2-amino-4- cyanobutanoyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.5 631 801 4-[(4-{[(2S)-2,3-diaminopropanoyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 440.5 632 802 N-[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}ethynyl)phenyl]piperidine-3-carboxamide 465.5 633 803 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({3- [(morpholin-4- ylacetyl)amino]phenyl}ethynyl)benzamide 481.5 634 804 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (pyrazin-2-ylethynyl)benzamide 341.3 635 805 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[3-(1H-imidazol-1- yl)propyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 519.6 636 806 N-((1S)-2-(hydroxyamino)-1-{[({[3-(1H- imidazol-1-yl)propyl]amino}acetyl)amino]methyl}-2- oxoethyl)-4-(phenylethynyl)benzamide 489.5 637 807 4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}ethynyl)benzoic acid 383.4 638 808 N-(2-{[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}ethynyl)phenyl]amino}- 2-oxoethyl)-1,3-benzodioxole-4- carboxamide 559.5 639 809 4-({4-[((2R)-2-{[(2R)-2,5- diaminopentanoyl]amino}-4- phenylbutanoyl)amino]phenyl}ethynyl)- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 629.7 640 810 4-[(4-{[(2R)-2-amino-4- phenylbutanoyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 515.6 641 811 4-[(4-{[(2S)-2-amino-3- phenylpropanoyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 501.6 642 812 4-{[4-({[(2-aminoethyl)amino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 454.5 643 813 N-{(1S)-2-(hydroxyamino)-1-[({[methyl(1- methylpiperidin-4-yl)amino]acetyl}amino)methyl]-2-oxoethyl}-4- (phenylethynyl)benzamide 492.6 644 814 4-[(4-{[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 465.5 645 815 4-[(4-{[(cyclopentylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 479.5 646 816 4-[(4-{[(cyclohexylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 493.6 647 817 4-[(4-{[(cycloheptylamino)acetyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 507.6 648 818 4-[(4-{[(cyclooctylamino)acetyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 521.6 649 819 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(propylamino)acetyl]amino}phenyl) ethynyl]benzamide 453.5 650 820 4-[(4-{[(hexylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 495.6 651 821 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(1-methylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 453.5 652 822 4-{[4-({[(1,1-dimethylethyl)amino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 467.5 653 823 4-{[4-({[ethyl(methyl)amino]acetyl}amino)phenyl]ethnyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 453.5 654 824 4-[(4-{[(diethylamino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 467.5 655 825 4-{[4-({[(1,1-dimethylethyl)(methyl) amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 481.6 656 826 4-{[4-({[cyclohexyl(methyl) amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 507.6 657 827 4-{[4-({[bis(1-methylethyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 495.6 658 828 4-{[4-({[(cyclohexylmethyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 507.6 659 829 4-{[4-({[(2,3-dimethylcyclohexyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 521.6 660 830 4-{[4-({[(1R,2R,4S)-bicyclo[2.2.1]hept-2- ylamino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 505.6 661 831 4-[(4-{[({[(1S,2R,5S)-6,6- dimethylbicyclo[3.1.1]hept-2-yl]methyl}amino)acetyl]amino}phenyl) ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 547.7 662 832 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[4-(trifluoromethyl)piperidin- 1-yl]acetyl}amino) phenyl]ethynyl}benzamide 547.5 663 833 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(2-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 504.5 664 834 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(2-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 521.0 665 835 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(2-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 500.6 666 836 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[2-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 516.6 667 837 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[2-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 554.5 668 838 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[({2-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 570.5 669 839 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(3-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 504.5 670 840 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(3-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 521.0 671 841 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(3-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 500.6 672 842 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[3-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 516.6 673 843 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[3-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 554.5 674 844 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[({3-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 570.5 675 845 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(4-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 504.5 676 846 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(4-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 521.0 677 847 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 500.6 678 848 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[4-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl) ethynyl]benzamide 516.6 679 849 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[4-(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 554.5 680 850 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[4-(1,1-dimethylethyl) phenyl]methyl}amino)acctyl]amino}phenyl)ethynyl]benzamide 542.6 681 851 N-{(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(1R)-1- phenylethyl]amino}acetyl)amino]phenyl}ethyl)benzamide 500.6 682 852 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4- [({[(1S)-1-phenylethyl]amino}acetyl)amino]phenyl}ethynyl) benzamide 500.6 683 853 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[(cyclahexylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 492.6 684 854 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]benzamide 450.5 685 855 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(cyclopentylamino)acetyl]amino}phenyl)ethynyl]benzamide 464.5 686 856 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(cyclohexylamino)acetyl]amino}phenyl)ethynyl]benzamide 478.6 687 857 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(cycloheptylamino)acetyl]amino}phenyl)ethynyl]benzamide 492.6 688 858 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(cyclooctylamino)acetyl]amino}phenyl)ethynyl]benzamide 506.6 689 859 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl[-4-[(4- {[(ethylamino)acetyl]amino}phenyl)ethynyl]benzamide 424.5 690 860 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(propylamino)acetyl]amino}phenyl)ethynyl]benzamide 438.5 691 861 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(butylamino)acetyl]amino}phenyl) ethynyl]benzamide 452.5 692 862 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(hexylamino)acetyl]amino}phenyl) ethynyl]benzamide 480.6 693 863 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4-({[(1- methylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 438.5 694 864 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[(1,1-dimethylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 452.5 695 865 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[ethyl(methyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 438.5 696 866 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[(diethylamino)acetyl]amino}phenyl) ethynyl]benzamide 452.5 697 867 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[(1,1-dimethylethyl)(methyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 466.6 698 868 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[cyclohexyl(methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 492.6 699 869 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[2-(2- fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.6 700 870 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[2-(3- fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.6 701 871 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[2-(4- fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.6 702 872 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(1S,2R)- 2-phenylcyclopropyl]amino}acetyl) amino]phenyl}ethynyl) benzamide 512.6 703 873 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(2,4- difluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 522.5 704 874 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(2,4- dichlorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 555.4 705 875 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4- {[({[4-fluoro-2-(trifluoromethyl) phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 572.5 706 876 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(2,5- difluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 522.5 707 877 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(3,4- difluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 522.5 708 878 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(3,4- dichlorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 555.4 709 879 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(3,4- dimethylphenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 514.6 710 880 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(3,5- difluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 522.5 711 881 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(3,5- dichlorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 555.4 712 882 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4-{[({[3,5- bis(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 622.5 713 883 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-({4-[({[(4- nitrophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 531.5 714 884 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4-{[(pyridin-2- ylamino)acetyl]amino}phenyl)ethynyl]benzamide 473.5 715 885 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4-{[(pyridin-3- ylamino)acetyl]amino}phenyl)ethynyl]benzamide 473.5 716 886 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4-({[(2- fluorophenyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 490.5 717 887 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4-({[(3- fluorophenyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 490.5 718 888 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4-({[(4- fluorophenyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 490.5 719 889 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-[(4-{[(pyridin-4- ylamino)acetyl]amino}phenyl) ethynyl]benzamide 473.5 720 890 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[(2,2,2-trifluoroethyl)amino]acetyl}amino)phenyl]ethnyl}benzamide 478.4 721 891 N-{(1S,2R).2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(pyridin-2-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 488.5 722 892 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(pyridin-3-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 488.5 723 893 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(pyridin-4-ylamino)acetyl]amino}phenyl)ethynyl]benzamide 488.5 724 894 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(4-phenylpiperazin-1- yl)acetyl]amino}phenyl) ethynyl]benzamide 556.6 725 895 4-{[4-({[4-(4-fluorophenyl) piperazin-1-yl]acetyl}amino) phenyl]ethynyl}-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 574.6 726 896 4-{[4-({[(1-acetylpiperidin-4- yl)(cyclopropyl)amino]acetyl}amino) phenyl]ethynyl}-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 576.7 727 897 4-[(4-{[(butylamino)acetyl]amino}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 467.5 728 898 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(1R)-1-phenylethyl]amino}acetyl)amino]phenyl}ethyl)benzamide 515.6 729 899 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(1S)-1-phenylethyl]amino}acetyl)amino]phenyl}ethyl)benzamide 515.6 730 900 4-{[4-({[cyclopropyl(methyl) amino]acetyl}amina)phenyl]ethynyl}-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 465.5 731 901 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-([4- ({[methyl(phenyhnethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 515.6 732 902 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4- {[4-({[cyclopropyl(methyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 450.5 733 903 4-[(4-{[(2S)-2-aminopropanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 425.5 734 904 4-[(4-{[(2R)-2-aminopropanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 425.5 735 905 4-[(4-{[(2S)-2-amino-3- methylbutanoyl]amino}phenyl) ethynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 453.5 736 906 4-[(4-{[(2S,3R)-2-amino-3- hydroxybutanoyl]amino}phenyl) ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 455.5 737 907 (2S)-N-[4-({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino) carbonyl]phenyl}ethynyl)phenyl]pyrrolidine-2-carboxamide 451.5 738 908 4-[(4-{[(2S)-2-amino-3-(1H- imidazol-4-yl)propanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 491.5 739 909 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(methyloxy)acetyl]amino}phenyl)ethynyl]benzamide 426.4

[0942] 66 Example Structure Name MH+ 740 910 4-[(4-{[(2S)-2-amino-3- methylbutanoyl]amino}phenyl)ethynyl]-N- [(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 438.5 741 911 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(3- phenylpropyl)amino]acetyl}amino)phenyl]ethnyl}benzamide 514.6 742 912 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(thien-2- ylethynyl)benzamide 345.4 743 913 4-({4-[((2S)-2-{[(2S)-2,5- diaminopentanoyl]amino}-3- phenylpropanoyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 615.7 744 914 3,4-dihydroxy-N-[(2S)-3-(hydroxyamino)-3- oxo-2-({[4-(phenylethynyl) phenyl]carbonyl}amino)propyl]benzamide 460.5 745 915 1,1-dimethylethyl 3-[(2-{[(2S)-3- (hydroxyamino)-3-oxo-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-2- oxoethyl)amino]propylcarbamate 538.6 746 916 N-[(1S)-2-(hydroxyamino)-1-({[(4- methylpiperazin-1-yl)acetyl]amino}methyl)-2-oxoethyl]-4- (phenylethynyl)benzamide 464.5 747 917 4-{[4-({2-[(2-aminoethyl)amino]-2- oxoethyl}oxy)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyammo)carbonyl]propyl}benzamide 455.5 748 918 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[3- (aminomethyl)phenyl]ethynyl}benzamide 353.4 749 919 1,1-dimethylethyl (2S)-3-(hydroxyamino)-2- [({4-[(4-{[2-(hydroxyamino)-2- oxoethyl]oxy}phenyl)ethynyl]phenyl}carbonyl)amino]-3- oxopropylcarbamate 513.5 750 920 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[2-(hydroxyamino)-2- oxoethyl]oxy}phenyl)ethynyl]benzamide 413.4 751 921 3,4-dihydroxy-N-(2-{[4-({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]amino}-2- oxoethyl)benzamide 547.5 752 922 4-({4-[({[(2S)-2,5- diaminopentanoyl]amino}acetyl) amino]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 525.6 753 923 4-[(4-{[(2-aminoethyl)amino]carbonyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 425.5 754 924 N-[(1S)-1-[({[(3-aminopropyl) amino]acetyl}amino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 438.5 755 925 3-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbanyl]propyl}amino) carbonyl]phenyl}ethynyl) benzoic acid 383.4 756 926 4-{[4-({[(3-aminopropyl)amino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 468.5 757 927 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(pyrazin-2-ylethynyl)benzamide 326.3 758 928 4-({3-[(4-aminobutanoyl)amino]phenyl}ethynyl)-N-[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 424.5 759 929 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4- [(4-{[(2S)-2,5-diaminopentanoyl]amino}phenyl)ethynyl]benzamide 453.5 760 930 4-({2-[(aminoacetyl)amino]phenyl}ethynyl)- N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 396.4 761 931 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[2-(ethylamino)-2- oxoethyl]phenyl}ethynyl)benzamide 409.5 762 932 4-({4-[(aminoacetyl)amino]-3- methylphenyl}ethynyl)-N-[(1S)-1- (animomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 410.4 763 933 4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)- 2-(hydroxyamino)-2- oxoethyl]-3-fluorobenzamide 414.4 764 934 N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]-4-{[4- ({[(cyanomethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 435.5 765 935 [4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl) phenyl]acetic acid 397.4 766 936 4-amino-2-({[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydraxyan-nno)carbonyl]propyl}amino) carbonyl]phenyl}ethynyl)phenyl]carbonyl}amino)-4- oxobutanoic acid 767 937 4-amino-2-[({[4-({4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]oxy}acetyl)amino]- 4-oxobutanoic acid 527.5 768 938 N-((1S)-2-(hydroxyamino)-1-{[(morpholin-4- ylacetyl)amino]methyl}-2-oxoethyl)-4- (phenylethynyl)benzamide 451.5 769 939 N-[(1S)-1-[({[2,3-dihydroxypropyl) thio]acetyl}amino)methyl]-2- (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 472.5 770 940 methyl (2S)-3-amino-2-({[4- (phenylethynyl)phenyl]carbonyl}amino) propanoate 323.4 771 941 N-{(1S)-2-(hydroxyamino)-2-oxo-1-[({[(2- phenylethyl)amino]acetyl}amino) methyl]ethyl}-4- (phenylethynyl)benzamide 485.6 772 942 4-[(4-{2-{(2-aminoethyl)amino]-2- oxoethyl}phenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 439.5 773 943 4-[(4-{[(6-aminohexyl)amino]carbonyl}phenyl)ethynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 481.6 774 944 4-[4-(4-{[(ethylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 463.5 775 945 4-[4-(4-{[(cyclopropylamino) acetyl]amino}phenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 475.5 776 946 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4- [(piperidin-1-ylacetyl)amino]phenyl}buta- 1,3-diynyl)benzamide 503.6 777 947 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[(phenylamino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 511.5 778 948 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[4- ({[(phenylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 525.6 779 949 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}4′- ethyl-1,1′-biphenyl-4-carboxamide 342.4 780 950 4-[(4-{[(dimethylamino)acetyl amino}phenyl)ethynl]-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 439.5 781 951 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[(pyrrolidin-1- ylacetyl)amino]phenyl}ethynyl)benzamide 465.5 782 952 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(pentylamino)acetyl]amino}phenyl)ethynyl]benzamide 481.6 783 953 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(thien-2-ylmethyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 507.6 784 954 4-{[4-({[(1H-benzimidazol-2- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 541.6 785 955 4-{[4-({[(1-benzothien-3- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 557.6 786 956 4-(4-{4-[({[(2-fluorophenyl)methyl]amino}acetyl)amino]phenyl}buta- 1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 543.6 787 957 4-(4-{4-[({[(3-fluorophenyl)methyl]amino}acctyl)amino]phenyl}buta- 1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 543.6 788 958 4-(4-{4-[({[(4-fluorophenyl)methyl]amino}acetyl)amino]phenyl}buta- 1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 543.6 789 959 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[({[(2-methylphenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 539.6 790 960 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[({[(3-methylphenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 539.6 791 961 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[({[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 539.6 792 962 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {4-[4-({[(pyridin-2- ylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 526.6 793 963 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {4-[4-({[(pyridin-3- ylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 526.6 794 964 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {4-[4-({[(pyridin-4- ylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 526.6 795 965 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [4-(4-{[{([2-(methyloxy) phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 555.6 796 966 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [4-(4-{[({[3-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 555.6 797 967 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [4-(4-{[({[4-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 555.6 798 968 4-{4-[4-({[(2-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 529.5 799 969 4-{4-[4-({[(3-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 529.5 800 970 4-{4-[4-({[(4-fluorophenyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 529.5 801 971 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[(pyridin-2-ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 512.5 802 972 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[(pyridin-3-ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 512.5 803 973 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[(pyridin-4-ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 512.5 804 974 4-[4-(4-{[(cyclobutylamino)acetyl]amino}phenyl)buta-1,3-diynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 489.5 805 975 4-[4-(4-{[(cyclopentylamino)acetyl]amino}phenyl)buta-1,3-diynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 503.6 806 976 4-[4-(4-{[(cyclohexylamino)acetyl]amino}phenyl)buta-1,3-diynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 517.6 807 977 4-[4-(4-{[(cycloheptylamino)acetyl]amino}phenyl)buta-1,3-diynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 531.6 808 978 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[(methylamino)acetyl]amino}phenyl buta-1,3-diynyl]benzamide 449.5 809 979 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[(propylamino)acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 477.5 810 980 4-[4-(4-{[(butylamino)acetyl]amino}phenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 491.6 811 981 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(4- {[(pentylamino)acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 505.6 812 982 4-[4-(4-{[(hexylamino)acetyl]amino}phenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 519.6 813 983 4-{4-[4-({[ethyl(methyl)amino]acetyl}amino)phenyl]buta- 1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 477.5 814 984 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {4-[4-({[(1-methylethyl)amino]acetyl}amino)phenyl]buta- 1,3-diynyl}benzamide 477.5 815 985 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {4-[4-({[(2-methylpropyl)amino]acetyl}amino)phenyl]buta- 1,3-diynyl}benzamide 491.6 816 986 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {4-[4-({[(2,2,2-trifluoroethyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}benzamide 517.5 817 987 4-{4-[4-({[(2-hydroxyethyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 479.5 818 988 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4- [({[2-(methyloxy)ethyl]amino}acetyl)amino]phenyl}buta-1,3- diynyl)benzamide 493.5 819 989 4-(4-{4-[({[2-(dimethylamino) ethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 506.6 820 990 4-{4-[4-({[(2-cyanoethyl)amino]acetyl}amino)phenyl]buta- 1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 488.5 821 991 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4- {4-[(pyrrolidin-1-ylacetyl) amino]phenyl}buta-1,3- diynyl)benzamide 489.5 822 992 4-(4-{4-[(azepan-1-ylacetyl) amino]phenyl}buta-1,3-diynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 517.6 823 993 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [4-(4-{[(4-methylpiperazin-1- yl)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 518.6 824 994 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[(morpholin-4-ylacetyl) amino]phenyl}buta-1,3- diynyl)benzamide 505.5 825 995 4-{4-[4-({[cyclohexyl(methyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 531.6 826 996 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[({[(1R)-1-phenylethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 539.6 827 997 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[({[(1S)-1-phenylethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 539.6 828 998 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {4-[4-({[(2-phenylethyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 539.6 829 999 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[(1H-imidazol-1-ylacetyl) amino]phenyl}buta- 1,3-diynyl)benzamide 486.5 830 1000 4-{4-[4-({[(1R,2R,4S)-bicyclo[2.2.1]hept-2- ylamino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 529.6 831 1001 4-{4-[4-({[(cyclohexylmethyl) amino]acetyl}amino)phenyl]buta- 1,3-diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 531.6 832 1002 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4′-ethyl-2-fluoro-1,1′- biphenyl-4-carboxamide 346.4 833 1003 4-({4-[(aminoacetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3- (methyloxy)benzamide 441.5 834 1004 4′-ethyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-2- (methyloxy)-1,1′-biphenyl-4-carboxamide 373.4 835 1005 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-3- (methyloxy)-4-(phenylethynyl)benzamide 369.4 836 1006 4-[(4-ethylphenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 367.4 837 1007 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- hydroxyphenyl)ethynyl]benzamide 355.4 838 1008 2-[(2-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4- (phenylethynyl)phenyl]carbonyl}amino) propyl]amino}-2-oxoethyl)thio]prapanoic acid 470.5 839 1009 4-amino-2-[(2-{[(2S)-3-(hydroxyamino)- 3-oxo-2-({[4-(phenylethynyl) phenyl]carbonyl}amino)propyl]amino}-2-oxoethyl)amino]-4- oxobutanoic acid 496.5 840 1010 1,1-dimethylethyl 4-amino-2-[(2-{[(2S)-3- (hydroxyamino)-3-oxo-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)propyl]amino}-2-oxoethyl) amino]-4-oxobutanoate 552.6 841 1011 2,6-dihydroxy-N-[(2S)-3-(hydroxyamino)- 3-oxo-2-({[4-(phenylethynyl) phenyl]carbonyl}amino)propyl]pyridine-4-carboxamide 461.4 842 1012 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- aminophenyl)ethynyl]benzamide 339.4 843 1013 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- ethylphenyl)ethynyl]benzamide 352.4 844 1014 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-ethylphenyl)ethynyl]- 3-fluorobenzamide 370.4 845 1015 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(3- aminopropanoyl)amino]phenyl}ethynyl)benzamide 410.4 846 1016 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- [(dimethylamino)acetyl]amino}phenyl) ethynl]benzamide 424.5 847 1017 4({4[(4-aminobutanoyl)amino]phenyl}ethynyl)-N-[(1S)- 1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 424.5 848 1018 N-{(1S)-2-(hydroxyamino)-1-[({[2- (methyloxy)phenyl]methyl}amino) methyl]-2-oxoethyl}-4-(phenylethynyl) benzamide 444.5 849 1019 N-[(1S)-1-[(diprop-2-enylamino)methyl]- 2-(hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 404.5 850 1020 N-[(1S)-2-(hydroxyamino)-1-({[({[2- (methoxy)phenyl]methyl}amino) acetyl]amino}methyl)-2- oxoethyl]-4-(phenylethynyl)benzamide 501.6 851 1021 N-((1S)-2-(hydroxyamino)-1-{[({[2- (methyloxy)phenyl]thio}acetyl)amino]methyl}-2-oxoethyl)-4- (phenylethynyl)benzamide 504.6 852 1022 (2S,3R)-3-amino-2-({[4-(phenylethynyl) phenyl]carbonyl}amino)butanoic acid 323.4 853 1023 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(4- {[(dimethylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 448.5 854 1024 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(4- {[(ethylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 448.5 855 1025 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(4- {[(cyclopropylamino)acetyl]amino}phenyl)buta-1,3-diynyl]benzamide 460.5 856 1026 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-(4-{4-[(piperidin-1- ylacetyl)amino]phenyl}buta-1,3- diynyl)benzamide 488.6 857 1027 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(4- {[(phenylamino)acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 496.5 858 1028 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{4-[4- ({[(phenylmethyl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}benzamide 510.6 859 1029 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(4- aminophenyl)buta-1,3- diynyl]benzamide 363.4 860 1030 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(pyrazin-2-ylamino) acetyl]amino}phenyl)ethynyl]benzamide 489.5 861 1031 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(4-phenylpiperidin-1- yl)acetyl]amino}phenyl) ethynyl]benzamide 555.6 862 1032 4-{[4-({[4-(2-fluorophenyl) piperazin-1-yl]acetyl}amino) phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 574.6 863 1033 4-{[4-({[(1S,4R)-bicyclo[2.2.1]hept-2- ylamino]acetyl}amino)phenyl]ethynyl}-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 505.6 864 1034 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(1S,2S,3S,5R)-2,6,6- trimethylbicyclo[3.1.1]hept-3- yl]amino}acetyl)amino]phenyl}ethynyl)benzamide 547.7 865 1035 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-([4- ({[(tricyclo[3.3.1.1˜3,7˜]dec-1- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 559.7 866 1036 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[(4- methylcyclohexyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 507.6 867 1037 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-([4- ({[(2,2,2-trifluoroethyl)amino]acetyl}amino)phenyl]ethnyl}benzamide 493.5 868 1038 4-({4-[({[2-(2-fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 533.6 869 1039 4-({4-[({[2-(3-fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 533.6 870 1040 4-({4-[({[2-(4-fluorophenyl)ethyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 533.6 871 1041 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(1S,2R)-2-phenylcyclopropyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 527.6 872 1042 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[({[(2- methylphenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 515.6 873 1043 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4-{[({[2- (trifluoromethyl)phenyl]methyl}amino) acetyl]amino}phenyl)ethynyl]benzamide 569.5 874 1044 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[({2-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 585.5 875 1045 4-({4-[({[(4-chlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 536.0 876 1046 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[({[4-(methyloxy)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 531.6 877 1047 4-[(4-{[({[4-(1,1-dimethylethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 557.7 878 1048 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}- 4-({4-[({[(4-nitrophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 546.5 879 1049 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 585.5 880 1050 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[({[4-(methylthio)phenyl]methyl}amino)acetyl]amino}phenyl) ethynyl]benzamide 547.6 881 1051 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[({4-[(trifluoromethyl)thio]phenyl}methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 601.6 882 1052 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[({[4-(methylsulfonyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 579.6 883 1053 4-({4-[({[(2,5-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 537.5 884 1054 4-({4-[({[(2,6-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 537.5 885 1055 4-({4-[({[(3,4-difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 537.5 886 1056 4-({4-[({[(3,4-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 570.4 887 1057 4-({4-[({[(3,4-dimethylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 529.6 888 1058 4-({4-[({[(3,5-dichlorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 570.4 889 1059 4-[(4-{[({[3,5-bis(trifluoromethyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 637.5 890 1060 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(2,3,4-trifluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.5 891 1061 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(2,4,5-trifluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.5 892 1062 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(3,4,5-trifluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 555.5 893 1063 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(pentylamino) acetyl]amino}phenyl)ethynyl]benzamide 466.6 894 1064 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(thien-2- ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 492.6 895 1065 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(4-phenylpiperidin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 540.6 896 1066 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(4-phenylpiperazin-1- yl)acetyl]amino}phenyl)ethynyl]benzamide 541.6 897 1067 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[(4-({[4-(2- fluorophenyl)piperazin-1- yl]acetyl}amino)phenyl]ethynyl}benzamide 559.6 898 1068 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[4-(4- fluorophenyl)piperazin-1- yl]acetyl}amino)phenyl]ethynyl}benzamide 559.6 899 1069 4-{[4-({[(1-acetylpiperidin-4- yl)(cyclopropyl)amino]acetyl}amino)phenyl]ethynyl}-N- [(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 561.7 900 1070 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(2,3- dimethylcyclohexyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 506.6 901 1071 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(1R,2R,4S)- bicyclo[2.2.1]hept-2- ylamino]acetyl}amino)phenyl]ethynyl}benzamide 490.6 902 1072 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[(1S,2R,5S)-6,6- dimethylbicyclo[3.1.1]hept-2- yl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 532.7 903 1073 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(1S,4R)-bicyclo[2.2.1]hept-2-ylamino]acetyl}amino) phenyl]ethynyl}benzamide 490.6 904 1074 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(1S,2S,3S,5R)-2,6,6- trimethylbicyclo[3.1.1]hept-3- yl]amino}acetyl)amino]phenyl}ethynyl)benzamide 532.7 905 1075 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[(tricyclo[3.3.1.1˜3,7˜]dec-1-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 544.7 906 1076 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,6- difluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl) benzamide 522.5 907 1077 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[4- (methylthio)phenyl]methyl}amino) acetyl]amino}phenyl)ethynyl]benzamide 532.6 908 1078 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[({[4- (methylsulfonyl)phenyl]methyl}amino)acetyl]amino}phenyl)ethynyl]benzamide 564.6 909 1079 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[({4- [(trifluoromethyl)thio]phenyl}methyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 586.6 910 1080 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[({4- [(trifluoromethyl)oxy]phenyl}methyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 570.5 911 1081 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,4,5- trifluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 540.5 912 1082 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(2,3,4- trifluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 540.5 913 1083 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({[(3,4,5- trifluorophenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 540.5 914 1084 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[(pyrrolidin-1- ylacetyl)amino]phenyl}buta-1,3- diynyl)benzamide 474.5 915 1085 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[(azepan-1- ylacetyl)amino]phenyl}buta-1,3- diynyl)benzamide 502.6 916 1086 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[(piperazin-1- ylacetyl)amino]phenyl}buta-1,3- diynyl)benzamide 489.5 917 1087 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(4-methylpiperazin-1- yl)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 503.6 918 1088 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[(morpholin-4- ylacetyl)amino]phenyl}buta-1,3- diynyl)benzamide 490.5 919 1089 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4- ({[cyclohexyl(methyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 516.6 920 1090 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(2- fluorophenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3- diynyl)benzamide 528.6 921 1091 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(3- fluorophenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3- diynyl)benzamide 528.6 922 1092 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(4- fluorophenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3- diynyl)benzamide 528.6 923 1093 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(2- methylphenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3- diynyl)benzamide 524.6 924 1094 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(3- methylphenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3- diynyl)benzamide 524.6 925 1095 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(4- methylphenyl)methyl]amino}acetyl) amino]phenyl}buta-1,3- diynyl)benzamide 524.6 926 1096 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(pyridin-2- ylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 511.6 927 1097 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(pyridin-3- ylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 511.6 928 1098 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(pyridin-4- ylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 511.6 929 1099 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[({[2- (methyloxy)phenyl]methyl}amino) acetyl]amino}phenyl) buta-1,3-diynyl]benzamide 540.6 930 1100 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[({[3- (methyloxy)phenyl]methyl}amino) acetyl]amino}phenyl)buta- 1,3-diynyl]benzamide 540.6 931 1101 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[{[4- (methyloxy)phenyl]methyl}amino) acetyl]amino}phenyl)buta- 1,3-diynyl]benzamide 540.6 932 1102 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2- fluorophenyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 514.5 933 1103 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(3- fluorophenyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 514.5 934 1104 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(4- fluorophenyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 514.5 935 1105 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(pyridin-2- ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 497.5 936 1106 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(pyridin-3- ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 497.5 937 1107 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(pyridin-4- ylamino)acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 497.5 938 1108 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cyclobutylamino) acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 474.5 939 1109 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cyclopentylamino) acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 488.6 940 1110 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(cyclohexylamino) acetyl]amino}phenyl)buta- 1,3-diynyl]benzamide 502.6 941 1111 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl[-4-[4-(4-{[(cycloheptylamino) acetyl]amino}phenyl)buta- 1,3-diynyl]benzamide 516.6 942 1112 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(methylamino) acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 434.5 943 1113 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(propylamino) acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 462.5 944 1114 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(butylamino) acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 476.5 945 1115 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(pentylamino) acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 490.6 946 1116 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-{[(hexylamino) acetyl]amino}phenyl)buta-1,3- diynyl]benzamide 504.6 947 1117 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[ethyl (methyl)amino]acetyl}amino)phenyl]buta-1,3-diynyl}benzamide 462.5 948 1118 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(1- methylethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 462.5 949 1119 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2- methylpropyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 476.5 950 1120 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2- hydroxyethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 464.5 951 1121 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[2- (methyloxy)ethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 478.5 952 1122 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[2- (dimethylamino)ethyl]amino}acetyl) amino]phenyl}buta-1,3- diynyl)benzamide 491.6 953 1123 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2- cyanoethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 473.5 954 1124 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(thien-2- ylmethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 516.6 955 1125 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(1R)-1- phenylethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 524.6 956 1126 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[({[(1S)-1- phenylethyl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 524.6 957 1127 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(2- phenylethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 524.6 958 1128 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-{4-[(1H-imidazol-1- ylacetyl)amino]phenyl}buta-1,3- diynyl)benzamide 471.5 959 1129 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(1R,2R,4S)- bicyclo[2.2.1]hept-2- ylamino]acetyl}amino)phenyl]buta-1,3- diynyl}benzamide 514.6 960 1130 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4- ({[(cyclohexyhnethyl)amino]acetyl}amino) phenyl]buta-1,3-diynyl}benzamide 516.6 961 1131 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(6- pipendin-1-ylpyridin-3-yl)ethynyl]benzamide 423.5 962 1132 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[6-(4- methylpiperazin-1-yl)pyridin-3- yl]ethynyl}benzamide 438.5 963 1133 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(6- piperazin-1-ylpyridin-3- yl)ethynyl]benzamide 424.5 964 1134 4-[(6-azepan-1-ylpyridin-3-yl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 437.5 965 1135 4-{[6-(cyclobutylamino)pyridin-3- yl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 409.5 966 1136 4-{[6-(cyclohexylamino)pyridin-3- yl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 437.5 967 1137 4-{[6-(butylamino)pyridin-3- yl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.5 968 1138 4-({6-[(2-hydroxyethyl)amino]pyridin-3- yl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 399.4 969 1139 4-[(6-{[2-(dimethylamino)ethyl]amino}pyridin-3-yl)ethynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 426.5 970 1140 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({6- [(phenylmethyl)amino]pyridin-3- yl}ethynyl)benzamide 445.5 971 1141 4-[(6-{[(4-fluorophenyl)methyl]amino}pyridin-3-yl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 463.5 972 1142 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[6- (pyridin-4-ylamino)pyridin-3- yl]ethynyl}benzamide 432.4 973 1143 4-[(6-chloropyridin-3-yl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 374.8 974 1144 1,1-dimethylethyl (2S)-2-[({4-[(4- ethylphenyl)ethynyl]phenyl}carbonyl) amino]-3-(hydroxyamino)-3- oxopropylcarbamate 452.5 975 1145 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxoethyl]amino}carbonyl)phenyl]buta-1,3-diynyl}benzamide 493.5 976 1146 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- (morpholin-4- ylmethyl)phenyl]ethynyl}benzamide 438.5 977 1147 4-[(4-{[(2-aminoethyl)amino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.5 978 1148 4-({4-[((2S)-2-amino-5- {[amino(imino)methyl]amino}pentanoyl)amino]phenyl}ethynyl)- N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 495.6 979 1149 (2S)-6-amino-2-({[4-({4-[({(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]carbonyl}amino)hexanoic acid 511.5 980 1150 (2S)-6-amino-2-({[4-({4-[({(1S,2R)- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]acetyl}amino)hexanoic acid 525.6 981 1151 5-{[(2S)-3-(hydroxyamino)-3-oxo-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)propyl]amino}- 5-oxopentanoic acid 438.4 982 1152 N-(2-aminoethyl)-N′-[(2S)-3- (hydroxyamino)-3-oxo-2-({[4- (phenylethynyl)phenyl]carbonyl}amino) propyl]pentanediamide 480.5 983 1153 N-[(1S)-1-[(2,6-dioxopiperidin-1-yl)methyl]-2- (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl)benzamide 420.4 984 1154 N,N′-bis[(2S)-3-(hydroxyamino)-3-oxo- 2-({[4-(phenylethynyl)phenyl]carbonyl}amino)propyl]pentanediamide 743.8 985 1155 N-((1S)-2-(hydroxyamino)-2-axo-1- {[({[(1S)-1-phenylethyl]amino}acetyl)amino]methyl}ethyl)- 4-(phenylethynyl)benzamide 485.6 986 1156 N-{(1S)-2-hydroxy-1- [(hydroxyamino)carbonyl]-2-methylpropyl}- 4-(phenylethynyl)benzamide 353.4 987 1157 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(6-piperidin-1- ylpyridin-3-yl)ethynyl]benzamide 408.5 988 1158 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(6-morpholin-4- ylpyridin-3-yl)ethynyl]benzamide 410.4 989 1159 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[6-(4- methylpiperazin-1-yl)pyridin- 3-yl]ethynyl}benzamide 423.5 990 1160 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(6-piperazin-1- ylpyridin-3-yl)ethynyl]benzamide 409.5 991 1161 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(6-azepan-1- ylpyridin-3-yl)ethynyl]benzamide 422.5 992 1162 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[6-(cyclobutylamino) pyridin-3-yl]ethynyl}benzamide 394.4 993 1163 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[6-(cyclohexylamino) pyridin-3-yl]ethynyl}benzamide 422.5 994 1164 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[6-(butylamino) pyridin-3-yl]ethynyl}benzamide 396.5 995 1165 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(6-{[2- (methyloxy)ethyl]amino}pyridin-3- yl)ethynyl]benzamide 398.4 996 1166 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- (piperidin-1-ylmethyl) phenyl]ethynyl}benzamide 436.5 997 1167 4-[(4-{[(2S)-2-amino-3-(4- aminophenyl)propanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 516.6 998 1168 4-((2S)-2-amino-3-{[4-({4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}ethynyl)phenyl]amino}-3- oxopropyl)benzoic acid 545.6 999 1169 573.6 1000 1170 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[1-(hydroxymethyl)-2- methylpropyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 497.6 1001 1171 4-[4-(3-aminophenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 378.4 1002 1172 4-[4-(3-{[(2-aminoethyl)amino]methyl}phenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 435.5 1003 1173 5-[(4-{[4-({[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]amino}carbonyl)phenyl]ethynyl}phenyl)amino]-5- oxopentanoic acid 453.5 1004 1174 N-(2-aminoethyl)-3-{4-[4-({[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxoethyl]amino}carbonyl)phenyl]buta- 1,3-diynyl}benzamide 434.5 1005 1175 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[3-(aminomethyl) phenyl]buta-1,3-diynyl}benzamide 377.4 1006 1176 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[3- (trifluoromethyl)phenyl]buta-1,3- diynyl}benzamide 416.4 1007 1177 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-buta-1,3-diynylbenzamide 272.3 1008 1178 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(2-methylphenyl)buta- 1,3-diynyl]benzamide 362.4 1009 1179 4-(4-{4-[(3-aminopropanoyl)amino]phenyl}buta-1,3-diynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 449.5 1010 1180 4-[4-(3-{[(aminoacetyl)amino]methyl}phenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 449.5 1011 1181 4-(4-{3-[(aminoacetyl)amino]phenyl}buta- 1,3-diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 435.4 1012 1182 4-[4-(4-{[(2S)-2-aminopropanoyl]amino}phenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 449.5 1013 1183 4-(4-{4-[(aminoacetyl)amino]phenyl}buta- 1,3-diynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 420.4 1014 1184 4-[4-(3-{[(aminoacetyl)amino]methyl}phenyl)buta-1,3- diynyl]-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 434.5 1015 1185 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-(4-{4-[(3- aminopropanoyl)amino]phenyl}buta-1,3- diynyl)benzamide 434.5 1016 1186 4-(4-{3-[(aminoacetyl)amino]phenyl}buta- 1,3-diynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 420.4 1017 1187 4-[(4-{[(2S)-2-amino-3-(4- hydroxyphenyl)propanoyl]amino}phenyl)ethynyl]-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 517.6 1018 1188 4-(4-{4-[(aminoacetyl)amino]phenyl}buta-1,3-diynyl)-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 435.4 1019 1189 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(butylamino)methyl]phenyl}ethynyl) benzamide 409.5 1020 1190 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-(piperidin-1- ylmethyl)phenyl]ethynyl}benzamide 421.5 1021 1191 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- formylphenyl)ethynyl]benzamide 352.4 1022 1192 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(methylsulfonyl)amino]phenyl}ethynyl) benzamide 432.5 1023 1193 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(methylsulfonyl)amino]phenyl}ethynyl) benzamide 417.5 1024 1194 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(phenylsulfonyl)amino]phenyl}ethynyl) benzamide 479.5 1025 1195 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-(4-{4- [(phenylsulfonyl)amino]phenyl}buta-1,3- diynyl)benzamide 503.5 1026 1196 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-(morpholin-4- ylmethyl)phenyl]ethynyl}benzamide 423.5 1027 1197 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(4-methylpiperazin-1- yl)methyl]phenyl}ethynyl)benzamide 436.5 1028 1198 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(2- hydroxyethyl)amino]methyl}phenyl) ethynyl]benzamide 397.4 1029 1199 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[2- (methylaxy)ethyl]amino}methyl)phenyl]ethynyl}benzamide 411.5 1030 1200 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(cyclohexylamino) methyl]phenyl}ethynyl)benzamide 435.5 1031 1201 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- {[(phenylmethyl)amino]methyl}phenyl)ethynyl]benzamide 443.5 1032 1202 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(6-chloropyridin-3- yl)ethynyl]benzamide 359.8 1033 1203 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4- {4-[({[6-(methyloxy)pyridin-3- yl]amino}acetyl)amino]phenyl}buta-1,3-diynyl)benzamide 542.6 1034 1204 4-{4-[4-({[(6-chloropyridin-3- yl)amino]acetyl}amino)phenyl]buta-1,3- diynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 547.0 1035 1205 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- (pyrrolidin-1- ylmethyl)phenyl]ethynyl}benzamide 422.5 1036 1206 4-({4-[(ethylamino)methyl]phenyl}ethynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 396.5 1037 1207 4-({4-[(dimethylamino)methyl]phenyl}ethynyl)- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 396.5 1038 1208 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[(4-methylpiperazin-1- yl)methyl]phenyl}ethynyl)benzamide 451.5 1039 1209 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[3-(1H-imidazol-1-yl) propyl]amino}methyl)phenyl]ethynyl}benzamide 476.5 1040 1210 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-(4-thien-2-ylbuta- 1,3-diynyl)benzamide 354.4 1041 1211 N,N,N-triethyl-2-{[4-(4-{4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}buta-1,3-diynyl)phenyl]amino}-2- oxoethanaminium 520.6 1042 1212 4-[4-(2-aminophenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 378.4 1043 1213 4-[4-(3-{[(2-aminoethyl)amino]methyl}phenyl)buta-1,3- diynyl]-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 420.5 1044 1214 4-buta-1,3-diynyl-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 287.3 1045 1215 4-[4-(4-{[(2S)-2-amino-4- methylpentanoyl]amino}phenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 491.6 1046 1216 (2S)-4-[4-(4-{4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}amino) carbonyl]phenyl}buta-1,3-diynyl) phenyl]pyrrolidine-2-carboxamide 475.5 1047 1217 (2S)-N-[4-(4-{4-[({(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}buta-1,3-diynyl) phenyl]piperidine-2-carboxamide 489.5 1048 1218 4-[4-(4-{[(2S)-2,3-diaminopropanoyl]amino}phenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.5 1049 1219 4-[4-(4-{[(2S)-2-amino-3-(1H-imidazol-nl 4-yl)propanoyl]amino}phenyl)buta- 1,3-diynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 515.5 1050 1220 N-[1-[(hydroxyamino)carbonyl]-2- (propylamino)propyl]-4-[(4- {[(propylamino)acetyl]amino}phenyl)ethynyl]benzamide 494.6 1051 1221 4-[(4-{[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]-N- {2-(cyclobutylamino)-1- [(hydroxyamino)carbonyl]propyl}benzamide 518.6 1052 1222 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(cyclopropylamino)acetyl]amino}phenyl)ethynyl]benzamide 450.5 1053 1223 1-[(1R,2S)-2-[({4-[(4- {[(cyclopropylamino)acetyl]amino}phenyl)ethynyl]phenyl}carbonyl) amino]-3-(hydroxyamino)-1- methyl-3-oxopropyl]triaza-1,2- dien-2-ium 477.5 1054 1224 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[(4-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.6 1055 1225 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({[(3-fluorophenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 518.6 1056 1226 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(propylamino)acetyl]amino}phenyl) ethynyl]benzamide 452.5 1057 1227 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[(phenylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 500.6 1058 1228 1-((1R,2S)-3-(hydroxyamino)-1-methyl- 3-oxo-2-{[(4-{[4-({[(phenylmethyl) amino]acetyl}amino)phenyl]ethynyl}phenyl)carbonyl]amino}propyl)triaza-1,2-dien-2-ium 527.6 1059 1229 N-{(1S,2R)-2-amino-1-[(hydroxyamino) carbonyl]propyl}-4-[(4- {[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]benzamide 464.5 1060 1230 1-[(1R,2S)-2-[({4-[(4- {[(cyclobutylamino)acetyl]amino}phenyl) ethynyl]phenyl}carbonyl)amino]-3- (hydroxyamino)-1-methyl-3-oxopropyl]triaza-1,2-dien-2-ium 491.5 1061 1231 4-[(4-ethylphenyl)ethynyl]-N-{(1S)-1- [(hydroxyamino)carbonyl]-2- methylpropyl}benzamide 365.4 1062 1232 4-(4-{4-(ethylamino)methyl]phenyl}buta-1,3- diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 420.5 1063 1233 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(3-aminophenyl)buta- 1,3-diynyl]benzamide 363.4 1064 1234 4-(4-{3-[(4-aminobutanoyl)amino]phenyl}buta-1,3-diynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 463.5 1065 1235 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(3- hydroxyphenyl)buta-1,3-diynyl]benzamide 379.4 1066 1236 4-(4-{2-[(aminoacetyl)amino]phenyl}buta-1,3- diynyl)-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 435.4 1067 1237 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[2,4-bis(methyloxy) pyrimidin-5-yl]buta- 1,3-diynyl}benzamide 410.4 1068 1238 (2S)-6-amino-2-{[(4-{4-[4-({[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxoethyl]amino}carbonyl)phenyl]buta-1,3- diynyl}phenyl)carbonyl]amino}hexanoic acid 520.6 1069 1239 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(2-aminophenyl)buta-1,3- diynyl]benzamide 363.4 1070 1240 4-[4-(4-{2-[(2-aminoethyl)amino]-2- oxoethyl}phenyl)buta-1,3-diynyl]-N- [(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 448.5 1071 1241 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(2-aminopyrimidin-5- yl)buta-1,3-diynyl]benzamide 365.4 1072 1242 4-(4-{3-[(4-aminobutanoyl)amino]phenyl}buta-1,3-diynyl)-N-[(1S)- 1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]benzamide 448.5 1073 1243 4-(4-{2-[(aminoacetyl)amino]phenyl}buta- 1,3-diynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 420.4 1074 1244 4-[4-(4-{2-[(2-aminoethyl)amino]-2- oxoethyl}phenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)caxbonyl]propyl}benzamide 463.5 1075 1245 4-[4-(4-{[(2,3-dihydroxypropyl)amino]methyl}phenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 466.5 1076 1246 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4- {4-[({[2-(methyloxy)phenyl]methyl}amino)methyl]phenyl}buta-1,3-diynyl)benzamide 512.6 1077 1247 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4- {4-[(pyridin-2-ylamino)methyl]phenyl}buta-1,3-diynyl)benzamide 469.5 1078 1248 4-[4-(4-{[(2-aminoethyl)amino]methyl}phenyl)buta-1,3-diynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 435.5 1079 1249 4-[(4-ethylphenyl)ethynyl]-N-[(1R)-1- [(ethylthio)methyl]-2- (hydroxyamino)-2-oxoethyl]benzamide 397.5 1080 1250 4-[(4-{[(2S)-2-aminopropanoyl]amino}phenyl)ethynyl]-N- [(1R)-1-[(ethylthio)methyl]-2- (hydroxyamino)-2-oxoethyl]benzamide 455.5 1081 1251 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(3-chlorophenyl)buta- 1,3-diynyl]benzamide 382.8 1082 1252 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[3-(methyloxy)phenyl]buta- 1,3-diynyl}benzamide 378.4 1083 1253 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{4-[(methylsulfonyl)amino]phenyl}buta-1,3-diynyl) benzamide 456.5 1084 1254 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- (4-{3-[(methylsulfonyl)amino]phenyl}buta-1,3-diynyl) benzamide 456.5 1085 1255 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-(4-pyrazin-2-ylbuta-1,3- diynyl)benzamide 350.3 1086 1256 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[4-(3- nitrophenyl)buta-1,3-diynyl]benzamide 408.4 1087 1257 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(3- {[(methylsulfonyl)amino]methyl}phenyl)ethynyl]benzamide 446.5 1088 1258 4-[(2-formylphenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 367.4 1089 1259 N-{(1R,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{(3- {[(methylsulfonyl)amino]methyl}phenyl)ethynyl]benzamide 446.5 1090 1260 4-({2-[(aminoacetyl)amino]phenyl}ethynyl)- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.4 1091 1261 N-{(1S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{4-[3- (morpholin-4-ylmethyl)phenyl]buta-1,3- diynyl}benzamide 462.5 1092 1262 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(methylamino)methyl]phenyl}ethynyl)benzamide 367.4 1093 1263 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(ethylamino)methyl]phenyl}ethynyl)benzamide 381.4 1094 1264 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(propylamino)methyl]phenyl}ethynyl)benzamide 395.5 1095 1265 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(pentylamino)methyl]phenyl}ethynyl)benzamide 423.5 1096 1266 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(hexylamino)methyl]phenyl}ethynyl)benzamide 437.6 1097 1267 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(1- methylethyl)amino]methyl}phenyl) ethynyl]benzamide 395.5 1098 1268 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(2- methylpropyl)amino]methyl}phenyl) ethynyl]benzamide 409.5 1099 1269 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(1,1- dimethylethyl)amino]methyl}phenyl) ethynyl]benzamide 409.5 1100 1270 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(dimethylamino)methyl]phenyl}ethynyl)benzamide 381.4 1101 1271 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[ethyl(methyl) amino]methyl}phenyl)ethynyl]benzamide 395.5 1102 1272 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[2- (dimethylamino)ethyl]amino}methyl)phenyl]ethynyl}benzamide 424.5 1103 1273 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[4- (dimethylamino)butyl]amino}methyl)phenyl]ethynyl}benzamide 452.6 1104 1274 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(2- cyanoethyl)amino]methyl}phenyl) ethynyl]benzamide 406.5 1105 1275 4-{[4-({[2-(acetylamino)ethyl]amino}methyl)phenyl]ethynyl}- N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 438.5 1106 1276 4-[(4-{[(2-aminoethyl)amino]methyl}phenyl)ethynyl]-N- [(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl]benzamide 396.5 1107 1277 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(3- hydroxypropyl)amino]methyl}phenyl) ethynyl]benzamide 411.5 1108 1278 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[3- (methyloxy)propyl]amino}methyl) phenyl]ethynyl}benzamide 425.5 1109 1279 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({methyl[2- (methylaxy)ethyl]amino}methyl) phenyl]ethynyl}benzamide 425.5 1110 1280 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[3-(2- oxopyrrolidin-1-yl)propyl]amino}methyl)phenyl]ethynyl}benzamide 478.6 1111 1281 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(3-morpholin-4- ylpropyl)amino]methyl}phenyl) ethynyl]benzamide 480.6 1112 1282 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(cyclopropylamino)methyl]phenyl}ethynyl)benzamide 393.5 1113 1283 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(cyclobutylamino)methyl]phenyl}ethynyl)benzamide 407.5 1114 1284 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(cyclopentylamino)methyl]phenyl}ethynyl)benzamide 421.5 1115 1285 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- (cycloheptylamino)methyl]phenyl}ethynyl)benzamide 449.6 1116 1286 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4- [(cyclooctylamino)methyl]phenyl}ethynyl)benzamide 463.6 1117 1287 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-(pyrrolidin-1- ylmethyl)phenyl]ethynyl}benzamide 407.5 1118 1288 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-(azepan-1- ylmethyl)phenyl]ethynyl}benzamide 435.5 1119 1289 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(3R)-3- (dimethylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]benzamide 450.6 1120 1290 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(3S)-3- (dimethylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]benzanude 450.6 1121 1291 4-[(4-{[(3R)-3-(acetylamino)pyrrohdin-1- yl]methyl}phenyl)ethynyl]-N-[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 464.5 1122 1292 4-[(4-{[(3S)-3-(acetylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]-N-[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 464.5 1123 1293 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-(1,4′-bipiperidin-1′- ylmethyl)phenyl]ethynyl}benzamide 504.6 1124 1294 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- {[(cyclohexylmethyl)amino]methyl}phenyl)ethynyl]benzamide 449.6 1125 1295 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4- [cyclohexyl(methyl)amino]methyl}phenyl)ethynyl]benzamide 449.6 1126 1296 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(1R)-1- phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 457.5 1127 1297 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(1S)-1- phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 457.5 1128 1298 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(thien-2- ylmethyl)amino]methyl}phenyl) ethynyl]benzamide 449.5 1129 1299 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(2- phenylethyl)amino]methyl}phenyl) ethynyl]benzamide 457.5 1130 1300 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(piperidin-3- ylamino)methyl]phenyl}ethynyl) benzamide 436.5 1131 1301 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(piperidin-4- ylamino)methyl]phenyl}ethynyl) benzamide 436.5 1132 1302 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(piperidin- 2-ylmethyl)amino]methyl}phenyl) ethynyl]benzamide 450.6 1133 1303 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(piperidin-3- ylmethyl)amino]methyl}phenyl) ethynyl]benzamide 450.6 1134 1304 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2R)- pyrrolidin-2-ylmethyl]amino}methyl)phenyl]ethynyl}benzamide 436.5 1135 1305 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2S)- pyrrolidin-2-ylmethyl]amino}methyl)phenyl]ethynyl}benzamide 436.5 1136 1306 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(pyrrolidin-3- ylamino)methyl]phenyl}ethynyl) benzamide 422.5 1137 1307 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2- fluorophenyl)methyl]amino}methyl) phenyl]ethynyl}benzamide 461.5 1138 1308 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(3- fluorophenyl)methyl]amino}methyl) phenyl]ethynyl}benzamide 461.5 1139 1309 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(4- fluorophenyl)methyl]amino}methyl) phenyl]ethynyl}benzamide 461.5 1140 1310 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(2- methylphenyl)methyl]amino}methyl) phenyl]ethynyl}benzamide 457.5 1141 1311 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(3- methylphenyl)methyl]amino}methyl) phenyl]ethynyl}benzamide 457.5 1142 1312 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(4- methylphenyl)methyl]amino}methyl) phenyl]ethynyl}benzamide 457.5 1143 1313 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[2- (methyloxy)phenyl]methyl}amino) methyl]phenyl}ethynyl)benzamide 473.5 1144 1314 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[3- (methyloxy)phenyl]methyl}amino) methyl]phenyl}ethynyl)benzamide 473.5 1145 1315 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[({[4- (methyloxy)phenyl]methyl}amino) methyl]phenyl}ethynyl)benzamide 473.5 1146 1316 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(phenylamino) methyl]phenyl}ethynyl)benzamide 429.5 1147 1317 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(pyridin-3- ylmethyl)amino]methyl}phenyl) ethynyl]benzamide 444.5 1148 1318 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(4-phenylpiperidin- 1-yl)methyl]phenyl}ethynyl)benzamide 497.6 1149 1319 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-[(4-phenylpiperazin- 1-yl)methyl]phenyl}ethynyl)benzamide 498.6 1150 1320 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(1R,2R,4S)- bicyclo[2.2.1]hept-2-ylamino]methyl}phenyl)ethynyl]benzamide 447.5 1151 1321 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({4-{({[(1S,2R,5S)-6,6- dimethylbicyclo[3.1.1]hept-2- yl]methyl}amino)methyl]phenyl}ethynyl)benzamide 489.6 1152 1322 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(4-{[(1S,4R)-bicyclo[2.2.1]hept-2-ylamino]methyl}phenyl) ethynyl]benzamide 447.5 1153 1323 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4-({[(1S,2S,3S,5R)-2,6,6- trimethylbicyclo[3.1.1]hept-3- yl]amino}methyl)phenyl]ethynyl}benzamide 489.6 1154 1324 1-((1R,2S)-3-(hydroxyamino)-1-methyl-3- oxo-2-{[(4-{[4-({[(pyridin-4- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}phenyl)carbonyl]amino}propyl)triaza-1,2-dien-2-ium 528.6 1155 1325 1-((1R,2S)-3-(hydroxyamino)-1-methyl-3- oxo-2-{[(4-{[4-({[(pyridin-3- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}phenyl)carbonyl]amino}propyl)triaza-1,2-dien-2-ium 528.6 1156 1326 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-([4- ({[(pyridin-4-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 501.6 1157 1327 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[(pyridin-3-ylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 501.6 1158 1328 N-[1-[(hydroxyamino)carbonyl]-2- (methylamino)propyl]-4-{[4- ({[(phenylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 514.6 1159 1329 4-[(4-{[(cyclobutylamino)acetyl]amino}phenyl)ethynyl]-N-[1- [(hydroxyamino)carbonyl]-2- (methylamino)propyl]benzamide 478.6 1160 1330 4-[(4-{[(2S)-2-aminopropanoyl]amino}phenyl)ethynyl]-N-[(1R)-1- {[ethyl(hydroxy)-lambda˜4˜- sulfanyl]methyl}-2-(hydroxyamino)-2- oxoethyl]benzamide 473.6 1161 1331 4-[(4-ethylphenyl)ethynyl]-N- hydroxybenzamide 266.3 1162 1332 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(2,4-difluorophenyl)buta- 1,3-diynyl]benzamide 384.4 1163 1333 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[(2- aminophenyl)ethynyl]benzamide 339.4 1164 1334 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(3- {[(methylsulfonyl)amino]methyl}phenyl) buta-1,3-diynyl]benzamide 455.5 1165 1335 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(3- {[(methylsulfonyl)amnio]methyl}phenyl) buta-1,3-diynyl]benzamide 455.5 1166 1336 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-({3- [(methylsulfonyl)amino]phenyl}ethynyl)benzamide 417.5 1167 1337 4-[(4-{[(2S)-2-aminopropanoyl]amino}phenyl)ethynyl]-N- hydroxybenzamide 324.4 1168 1338 4-[(2-{[(2-aminoethyl)amino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.5 1169 1339 N-{(1R,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4- (phenylethynyl)benzamide 338.4 1170 1340 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4- [4-(4-aminophenyl)buta-1,3- diynyl]benzamide 377.4 1171 1341 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(3-hydroxyphenyl)buta- 1,3-diynyl]benzamide 364.4 1172 1342 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{4-[3-(morpholin-4- ylmethyl)phenyl]buta-1,3-diynyl}benzamide 447.5 1173 1343 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[({[2-(methyloxy)phenyl]methyl}amino)methyl]phenyl}ethynyl)benzamide 488.6 1174 1344 4-[(4-{[(2,3-dihydroxypropyl)amino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 442.5 1175 1345 4-({2-[(dimethylamino)methyl]phenyl}ethynyl)-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 396.5 1176 1346 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(methylamino)methyl]phenyl}ethynyl)benzamide 382.4 1177 1347 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(propylamino)methyl]phenyl}ethynyl)benzamide 410.5 1178 1348 4-({4-[(butylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 424.5 1179 1349 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [(pentylamino)methyl)phenyl}ethynyl)benzamide 438.5 1180 1350 4-({4-[(hexylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 452.6 1181 1351 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(1-[(hydroxyamino) carbonyl]propyl}-4-[(4-{[(1- methylethyl)amino]methyl}phenyl) ethynyl]benzamide 410.5 1182 1352 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(2-methylpropyl) amino]methyl}phenyl)ethynyl]benzamide 424.5 1183 1353 4-[(4-{[(1.1-dimethylethyl)amino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 424.5 1184 1354 4-[(4-{[ethyl(methyl)amino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 410.5 1185 1355 4-{[4-({[(2-(dimethylamino)ethyl]amino}methyl)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 439.5 1186 1356 4-{[4-({[4-(dimethylamino)butyl]amino}methyl)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 467.6 1187 1357 4-[(4-{[(2-hydroxyethyl)amino]methyl}phenyl)ethynyl]- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 412.5 1188 1358 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-[(4- {[(3-hydroxypropyl)amino]methyl}phenyl)ethynyl]benzamide 426.5 1189 1359 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({methyl[2-(methyloxy)ethyl]amino}methyl)phenyl]ethynyl}benzamide 440.5 1190 1360 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[2- (methyloxy)ethyl]axmno}methyl) phenyl]ethynyl}benzamide 426.5 1191 1361 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4-({[3- (methyloxy)propyl]amino}methyl) phenyl]ethynyl}benzamide 440.5 1192 1362 4-[(4-{[(2-cyanoethyl)amino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 421.5 1193 1363 4-{[4-({[2-(acetylamino)ethyl]amino}methyl)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 453.5 1194 1364 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[3-(2-oxopyrrolidin-1- yl)propyl]amino}methyl) phenyl]ethynyl}benzamide 493.6 1195 1365 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(3-morpholin-4- ylpropyl)amino]methyl}phenyl) ethynyl]benzamide 495.6 1196 1366 4-({4-[(cyclopropylamino)methyl]phenyl}ethynyl)-N-{(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 408.5 1197 1367 4-({4-[(cyclobutylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 422.5 1198 1368 4-({4-[(cyclopentylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 436.5 1199 1369 4-({4-[(cyclohexylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 450.5 1200 1370 4-({4-[(cycloheptylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.6 1201 1371 4-({4-[(cyclooctylamino)methyl]phenyl}ethynyl)-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 478.6 1202 1372 4-{[4-(azepan-1-ylmethyl)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 450.5 1203 1373 4-[(4-{[(3R)-3-(dimethylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 465.6 1204 1374 4-[(4-{[(3S)-3-(dimethylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 465.6 1205 1375 4-[(4-{[(3R)-3-(acetylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 479.5 1206 1376 4-[(4-{[(3S)-3-(acetylamino)pyrrolidin-1- yl]methyl}phenyl)ethynyl]-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 479.5 1207 1377 4-{[4-(1,4′-bipiperidin-1′- ylmethyl)phenyl]ethynyl}-N-{(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 519.7 1208 1378 4-[(4-{[(cyclohexylmethyl)amino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 464.6 1209 1379 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4-[(4- phenylpiperazin-1- yl)methyl]phenyl}ethynyl)benzamide 513.6 1210 1380 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(2-phenylethyl)amino]methyl}phenyl)ethynyl]benzamide 472.6 1211 1381 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(1R)-1-phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1212 1382 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(1S)-1-phenylethyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1213 1383 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(thien-2-ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 464.6 1214 1384 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[(piperidin-3-ylamino) methyl]phenyl}ethynyl)benzamide 451.5 1215 1385 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[(piperidin-4-ylamino) methyl]phenyl}ethynyl)benzamide 451.5 1216 1386 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(piperidin-2-ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 465.6 1217 1387 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(piperidin-3-ylmethyl)amino]methyl}phenyl)ethynyl]benzamide 465.6 1218 1388 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(2R)-pyrrolidin-2- ylmethyl]amino}methyl)phenyl]ethynyl}benzamide 451.5 1219 1389 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(2S)-pyrrolidin-2- ylmethyl]amino}methyl)phenyl]ethynyl}benzamide 451.5 1220 1390 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[(pyrrolidin-3- ylamino)methyl]phenyl}ethynyl) benzamide 437.5 1221 1391 4-{[4-({[(2-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 476.5 1222 1392 4-{[4-({[(3-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbanyl]propyl}benzamide 476.5 1223 1393 4-{[4-({[(4-fluorophenyl)methyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)- 2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide 476.5 1224 1394 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(2-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1225 1395 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(3-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1226 1396 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- {[4-({[(4-methylphenyl)methyl]amino}methyl)phenyl]ethynyl}benzamide 472.6 1227 1397 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(phenylmethyl)amino]methyl}phenyl)ethynyl]benzamide 458.5 1228 1398 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- ({4-[(phenylamino)methyl]phenyl}ethynyl)benzamide 444.5 1229 1399 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4- [(4-{[(pyridin-3-ylmethyl) amino]methyl}phenyl)ethynyl]benzamide 459.5 1230 1400 4-[(4-{[(1R,2R,4S)-bicyclo[2.2.1]hept-2- ylamino]methyl}phenyl)ethynyl]-N- {(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 462.6 1231 1401 (3R)-N-hydroxy-3-({[4- (phenylethynyl)phenyl]carbonyl}amino) piperidine-3-carboxamide 364.4 1232 1402 4-({[4-(phenylethynyl)phenyl]carbonyl}amino)piperidine-4- carboxylic acid 349.4 1233 1403 N-{(1S)-2-(hydroxyamino)-2-oxo-1-[(2S)- pyrrolidin-2-ylmethyl]ethyl}-4- (phenylethynyl)benzamide 378.4 1234 1404 (3R)-3-{[(4-ethyl-1,1′-biphenyl-4- yl)carbonyl]amino}-N- hydroxypiperidine-3-carboxamide 368.4 1235 1405 1,1-dimethylethyl 3-(4-{4-[({(1S,2R)-2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}amino)carbonyl]phenyl}buta-1,3-diynyl) phenylcarbamate 478.5 1236 1406 4-[4-(3-amino-4-methylphenyl)buta-1,3- diynyl]-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 392.4 1237 1407 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(3-amino-4-methylphenyl) buta-1,3-diynyl]benzamide 377.4 1238 1408 4-(4-{4-[(aminoacetyl)amino]-3- methylphenyl}buta-1,3-diynyl)-N-[(1S)-1- (aminomethyl)-2-(hydroxyamino)-2- oxoethyl]benzamide 434.5 1239 1409 N-{(1S,2R)-2-amino-1- [(hydroxyamino)carbonyl]propyl}-4-(2- phenylethenyl)benzamide 340.4 1240 1410 N-[(2R)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4′-ethyl-1,1′-biphenyl-4- carboxamide 328.4 1241 1411 N-[(2R)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4-(phenylethynyl) benzamide 324.4 1242 1412 N-[(2R)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4-(4- chlorophenyl)cyclohexanecarboxamide 340.8 1243 1413 N-[(2S)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4-(4- chlorophenyl)cyclohexanecarboxamide 340.8 1244 1414 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[2-(4- methylphenyl)ethyl]benzamide 342.4 1245 1415 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-[4-(4- aminophenyl)butyl]benzamide 371.4 1246 1416 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[methyl(pyridin-2- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 516.6 1247 1417 4-{[4-({[[(2-fluorophenyl)methyl](methyl) amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 533.6 1248 1418 4-{[4-({[[(3-fluorophenyl)methyl](methyl) amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 533.6 1249 1419 4-{[4-({[[(4-fluorophenyl)methyl](methyl) amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 533.6 1250 1420 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[[(2- fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 518.6 1251 1421 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[[(3- fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 518.6 1252 1422 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[[(3- fluorophenyl)methyl](methyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 518.6 1253 1423 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({methyl[(2- methylphenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 514.6 1254 1424 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[({methyl[(4- methylphenyl)methyl]amino}acetyl) amino]phenyl}ethynyl)benzamide 514.6 1255 1425 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4- ({[methyl(phenylmethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 500.6 1256 1426 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[methyl(propyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 467.5 1257 1427 4-{[4-({[butyl(methyl)amino]acetyl}amino)phenyl]ethynyl}- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 481.6 1258 1428 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- {[methyl(pentyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 495.6 1259 1429 4-{[4-({[hexyl(methyl) amino]acetyl}amino)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 509.6 1260 1430 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[methyl(1-methylethyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 467.5 1261 1431 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- ({[methyl(2-methylpropyl)amino]acetyl}amino)phenyl]ethynyl}benzamide 481.6 1262 1432 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({methyl[(2-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 529.6 1263 1433 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-({4- [({methyl[(4-methylphenyl)methyl]amino}acetyl)amino]phenyl}ethynyl)benzamide 529.6 1264 1434 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(propyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 452.5 1265 1435 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[butyl(methyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 466.6 1266 1436 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(pentyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 480.6 1267 1437 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[hexyl(methyl) amino]acetyl}amino)phenyl]ethynyl}benzamide 494.6 1268 1438 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(1- methylethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 452.5 1269 1439 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(2- methylpropyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 466.6 1270 1440 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[methyl(pyridin-2- ylmethyl)amino]acetyl}amino) phenyl]ethynyl}benzamide 501.6 1271 1441 4-{[4-({[(3,4-dihydroxyphenyl) methyl]amino}methyl)phenyl]ethynyl}-N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 490.5 1272 1442 4-({2-[(aminoacetyl)amino]phenyl}ethynyl)-N- {(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 411.4 1273 1443 4-[(4-{[(2S)-2-aminopropanoyl]amino}phenyl)ethynyl]-N- {(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 425.5 1274 1444 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)- 2-oxoethyl]-4-{[4- (diethylamino)phenyl]ethynyl}benzamide 395.5 1275 1445 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-(ethylamino)phenyl]buta-1,3-diynyl}benzamide 391.4 1276 1446 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[(4-{[(2-amino-2- oxoethyl)amino]methyl}phenyl) ethynyl]benzamide 410.4 1277 1447 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4-({[1-(hydroxymethyl)-2- methylpropyl]amino}methyl)phenyl]ethynyl}benzamide 439.5 1278 1448 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-({4-[(pyridin-2- ylamino)methyl]phenyl}ethynyl) benzamide 430.5 1279 1449 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[3-(ethylamino)phenyl]buta-1,3-diynyl}benzamide 391.4 1280 1450 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[3- (ethylamino)phenyl]ethynyl}benzamide 367.4 1281 1451 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4- (hydroxymethyl)phenyl]ethynyl}benzamide 354.4 1282 1452 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[3- (diethylamino)phenyl]ethynyl}benzamide 395.5 1283 1453 N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-{[4- (morpholin-4- ylmethyl)phenyl]ethynyl}benzamide 438.5 1284 1454 4-({4-[(dimethylamino)methyl]phenyl}ethynyl)-N-{(1S,25)-2- hydroxy-1-[(hydroxyamino)carbonyl]propyl}benzamide 396.5 1285 1455 4-[(4-aminophenyl)ethynyl]-N-{(1S,2S)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 354.4 1286 1456 4-[4-(4-aminophenyl)buta-1,3-diynyl]-N- {(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 378.4 1287 1457 1,1-dimethylethyl 4-(4-{4-[({(1S,2R)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}amino) carbonyl]phenyl}buta-1,3- diynyl)phenylcarbamate 478.5 1288 1458 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-({[1-(hydroxymethyl)-2- methylpropyl]amino}methyl)phenyl]buta-1,3-diynyl}benzamide 463.5 1289 1459 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-[4-(4-hydroxyphenyl)buta-1,3- diynyl]benzamide 364.4 1290 1460 4-[(2,4-difluorophenyl)ethynyl]-N-{(1S,2S)-2- hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 375.3 1291 1461 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4-(morpholin-4- ylmethyl)phenyl]buta-1,3-diynyl}benzamide 447.5 1292 1462 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{4-[4- (hydroxymethyl)phenyl]buta-1,3- diynyl}benzamide 378.4 1293 1463 4-({3-[(2-aminoethyl)amino]phenyl}ethynyl)- N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}benzamide 397.4 1294 1464 N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl]-4-{[4- (trifluoromethyl)phenyl]ethynyl}benzamide 392.3 1295 1465 (2S,3R)-3-hydroxy-2-({[4- (phenylethynyl)phenyl]carbonyl}amino)butanoic acid 324.3 1296 1466 N-{(1S,2R)-1-{[(2- aminoethyl)amino]carbonyl}-2- hydroxypropyl)-4-(phenylethynyl)benzamide 366.4 1297 1467 1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-({[4-(4-phenylbuta-1,3- diynyl)phenyl]carbonyl}amino) propylcarbamate 448.5 1298 1468 N-{(1S,2R)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4-{4-[(3- morpholin-4-ylpropyl)amino]phenyl}buta-1,3-diynyl)benzamide 505.6 1299 1469 N-[(1S,2R)-2-hydroxy-1-({[2- (methylthio)phenyl]amino}carbonyl) propyl]-4-(phenylethynyl)benzamide 445.6 1300 1470 N-{(1S,2R)-2-hydroxy-1-[(pyridin-2- ylamino)carbonyl]propyl}-4- (phenylethynyl)benzamide 400.4 1301 1471 N-((1S)-1-(aminomethyl)-2-{[(1,1- dimethylethyl)oxy]amino}-2-oxoethyl)-4-(4- phenylbuta-1,3-diynyl)benzamide 404.5 1302 1472 N-{(1S,2S)-2-hydroxy-1- [(hydroxyamino)carbonyl]propyl}-4-(4- phenylbuta-1,3-diynyl)benzamide 363.4 1303 1473 (2S,3R)-N,3-dihydroxy-2-({[4-(4-phenylbuta- 1,3-diynyl)phenyl]methyl}amino)butanamide 349.4 1304 1474 1,1-dimethylethyl (2S)-3-(hydroxyamino)-3- oxo-2-({[4-(4-phenylbuta-1,3- diynyl)phenyl]methyl}amino) propylcarbamate 434.5 1305 1475 (2S)-3-amino-N-hydroxy-2-({[4-(4- phenylbuta-1,3-diynyl)phenyl]methyl}amino)propanamide 334.4 1306 1476 N-[(1S)-2-(hydroxyamino)-1-(hydroxymethyl)- 2-oxoethyl]-4- [(trifluoromethyl)oxy]benzamide 309.2 1307 1477 N-{2-hydroxy-1-[(hydroxyamino)carbonyl]-2- phenylethyl}-4- [(trifluoromethyl)oxy]benzamide 385.3

Claims

1. A compound according to the formula I:

1478

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof,

wherein

E is absent or selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted C2-C6-alkenyl,

(4) substituted or unsubstituted C2-C6-alkynyl,

(5) substituted or unsubstituted aryl,

(6) substituted or unsubstituted heterocyclyl, and

(7) substituted or unsubstituted heteroaryl;

L is absent or selected from the group consisting of

(1) substituted or unsubstituted C1-C6-alkyl,

(2) —(NH)0-1—C(CH2)j—NR3L—(CH2)k—,

(3) —(NH)0-1—C(R1L, R2L)—NR3L—C(R1L, R2L)—,

(4) —C(R1L, R2L)—O—(R1L, R2L)—,

(5) —(CH2)j—NR3L—C(R1L, R2L)—CONH—(CH2)k—,

(6) —CO—C(R1L, R2L)—NHCO—,

(7) —CONH—,

(8) —NHCO—,

wherein

R1L, R2L, and R3L are independently selected from the group consisting of

(a) H,

(b) substituted or unsubstituted C1-C6-alkyl,

(c) C1-C6-alkyl substituted with aryl,

(d) C1-C6-alkyl substituted with heterocyclyl, and

(e) C1-C6-alkyl substituted with heteroaryl,

or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S,

j is an integer of 0-4;

k is an integer of 0-4;

D is absent or selected from the group consisting of

(1) substituted or unsubstituted C3-C8-cycloalkyl,

(2) substituted or unsubstituted aryl,

(3) substituted or unsubstituted heterocyclyl, and

(4) substituted or unsubstituted heteroaryl;

G is absent or selected from the group consisting of

(1) —(CH2)i—O—(CH2)i—,

(2) —(CH2)i—S—(CH2)i—,

(3) —(CH2)i—NRg—(CH2)i—,

(4) —C(═O)—,

(5) —NHC(═O)—,

(6) —C(═O)NH—,

(7) —(CH2)iNHCH2C(═O)NH—,

(8) —C≡C—,

(9) —C≡C—C≡C—, and

(10) —C═C—;

wherein

Rg is H or substituted or unsubstituted C1-C6-alkyl;

i is an interger of 0-4;

Y is selected from the group consisting of

(1) substituted or unsubstituted C3-C8-cycloalkyl,

(2) substituted or unsubstituted aryl,

(3) substituted or unsubstituted heterocyclyl, and

(4) substituted or unsubstituted heteroaryl;

X is selected from the group consisting of

(1) —(C═O)—,

(2) —C1-C6-alkyl-(C═O)—,

(3) —C2-C6-alkenyl-C═O)—,

(4) —C2-C6-alkynyl-C═O)—, and

(5) —CH2—;

or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

B is a absent or

1479

wherein R1b and R2b, are independently selected from the group consisting of

(a) H,

(b) substituted or unsubstituted C1-C6-alkyl,

(c) substituted or unsubstituted C2-C6-alkenyl,

(d) substituted or unsubstituted C2-C6-alkynyl,

(e) substituted or unsubstituted aryl,

(f) substituted or unsubstituted heterocyclyl,

(g) substituted or unsubstituted heteroaryl,

(h) C1-C6-alkyl substituted with aryl,

(i) C1-C6-alkyl substituted with heterocyclyl, and

(j) C1-C6-alkyl substituted with heteroaryl,

or R1b and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

q is an integer of 0-4;

R3 is H or substituted or unsubstituted C1-C6-alkyl,

or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S;

R4 is H or substituted or unsubstituted C1-C6-alkyl,

or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

n is an integer of 0-2;

A is selected from the group consisting of

(1) H,

(2) —(CH2)rC(R1a, R2a)(CH2)sOR3a,

(3) —(CH2)rC(R1a, R2a)N(R4a, R5a),

(4) —(CH2)rC(R1a, R2a)N(R4a)COR3a,

(5) —(CH2)rC(R1a, R2a)NHCON(R4a, R5a),

(6) —(CH2)rC(R1a, R2a)NHC(═NH)N(R4a, R5a),

(7) —CH(R1a, R2a),

(8) —C≡CH,

(9) —(CH2)rC(R1a, R2a)CN,

(10) —(CH2)rC(R1a, R2a)CO2R3a, and

(11) —(CH2)rC(R1a, R2a)CN(R4a, R5a),

wherein R1a, R2a, R3a, R4a, and R5a are independently selected from the group consisting of

(a) H,

(b) substituted or unsubstituted C1-C6-alkyl,

(c) substituted or unsubstituted aryl,

(d) substituted or unsubstituted heterocyclyl,

(e) substituted or unsubstituted heteroaryl,

(f) C1-C6-alkyl substituted with aryl,

(g) C1-C6-alkyl substituted with heterocyclyl, and

(h) C1-C6-alkyl substituted with heteroaryl,

or R4a and R5a together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

r is an integer of 0-4;

s is an integer of 0-4;

Q is absent or selected from the group consisting of

(1) —C(═O)N(R1, R2),

(2) —NHC(═O)N(R1, R2),

(3) —N(OH)C(═O)N(R1, R2),

(4) —CH(OH)C(═O)N(R1, R2),

(5) —CH[N(R2q, R3q)]C(═O)N(R1, R2),

(6) —CHR1qC(═O)N(R1, R2),

(7) —CO2H,

(8) —C(═O)NHSO2R4q,

(9) —SO2NH2,

(10) —N(OH)C(═O)R1q,

(11) —N(OH)SO2R4q,

(12) —NHSO2R4q,

(13) —SH,

(14) —CH(SH)(CH2)0-1C(═O)N(R1, R2),

(15) —CH(SH)(CH2)0-1CO2H,

(16) —CH(OH)(CH2)0-1CO2H,

(17) —CH(SH)CH2CO2R1q,

(18) —CH(OH)(CH2)SO2NH2,

(19) —CH(CH2SH)NHCOR1q,

(20) —CH(CH2SH)NHSO2R4q,

(21) —CH(CH2SR5q)CO2H,

(22) —CH(CH2SH)NHSO2NH2,

(23) —CH(CH2OH)CO2H,

(24) —CH(CH2OH)NHSO2NH2,

(25) —C(═O)CH2CO2H,

(26) —C(═O)(CH2)0-1CONH2,

(27) —OSO2NHR5q,

(28) —SO2NNNH2,

(29) —P(═O)(OH)2,

1480

(30)

(31)

(32)

R1 is selected from the group consisting of

(1) —H,

(2) —OH,

(3) —OC1-6-alkyl,

(4) —N(R2q, R3q), and

(5) substituted or unsubstituted C1-6-alkyl;

R2 is selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted C2-C6-alkenyl,

(4) substituted or unsubstituted C2-C6-alkenyl,

(5) substituted or unsubstituted aryl,

(6) substituted or unsubstituted heterocyclyl,

(7) substituted or unsubstituted heteroaryl,

(8) C1-C6-alkyl substituted with aryl,

(9) C1-C6-alkyl substituted with heterocyclyl, and

(10) C1-C6-alkyl substituted with heteroaryl,

or R1 and R2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,

R1q, R2q, R3q, R4q, and R5q are selected from H or C1-C6 alkyl,

wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

2. A compound of claim 1, wherein

wherein

E is absent or selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl, and

(5) substituted or unsubstituted heteroaryl;

L is absent or selected from the group consisting of

(1) —(CH2)j—NR3L—(CH2)k—,

(2) —C(R1L, R2L)j—NR3L—C(R1L, R2L)k—,

(3) —C(R1L, R2L)j—O—C(R1L, R2L)k—,

(4) —(CH2)j—NR3L—C(R1L, R2L)k—CONH—(CH2)k—,

(5) —CO—C(R1L, R2L)—NHCO—,

(6) —CONH—, and

(7) —NHCO—,

wherein

R1L, R2L, R3L are independently selected from the group consisting of

(a) H,

(b) substituted or unsubstituted C1-C6-alkyl,

(c) C1-C6-alkyl substituted with aryl,

(d) C1-C6-alkyl substituted with heterocyclyl,

(e) C1-C6-alkyl substituted with heteroaryl,

or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

j is an integer of 0-4;

k is an integer of 0-4;

D is absent or selected from the group consisting of

(1) substituted or unsubstituted C3-C8-cycloalkyl,

(2) substituted or unsubstituted aryl,

(3) substituted or unsubstituted heterocyclyl,

(4) substituted or unsubstituted heteroaryl, and

G is absent or selected from the group consisting of

(1) —C(═O)—,

(2) —NHC(═O)—,

(3) —C(═O)NH—,

(4) —(CH2)iNHCH2C(═O)NH—,

(5) —C≡C—, and

(6) —C≡C—C≡C—,

wherein i is an interger of 0-4;

Y is selected from the group consisting of

(1) substituted or unsubstituted C3-C8-cycloalkyl,

(2) substituted or unsubstituted aryl,

(3) substituted or unsubstituted heterocyclyl, and

(4) substituted or unsubstituted heteroaryl;

X is selected from the group consisting of

(1) —(C═O)—,

(2) —C1-C6-alkyl-(C═O)—,

(3) —C2-C6-alkenyl-(C═O)—,

(4) —C2-C6-alkynyl-(C═O)—, and

(5) —CH2—;

or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

B is absent or

1481

wherein R1b and R2b are independently selected from the group consisting of

(a) H

(b)) substituted or unsubstituted C1-C6-alkyl,

(c) substituted or unsubstituted C2-C6-alkenyl,

(d) substituted or unsubstituted C2-C6-alkenyl,

(e) substituted or unsubstituted aryl,

(f) substituted or unsubstituted heterocyclyl,

(g) substituted or unsubstituted heteroaryl,

(h) C1-C6-alkyl substituted with aryl,

(i) C1-C6-alkyl substituted with heterocyclyl, and

(j) C1-C6-alkyl substituted with heteroaryl,

or R1b and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

q is an integer of 0-2;

R3 is H or substituted or-unsubstituted C1-C6-alkyl,

or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S;

R4 is H or substituted or unsubstituted C1-C6-alkyl,

or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

A is selected from the group consisting of

(1) H,

(2) —(CH2)rC(R1a, R2a)(CH2)sOR3a,

(3) —(CH2)rC(R1a, R2a)N(R4a, R5a),

(4) —(CH2)rC(R1a, R2a)N(R4a)COR3a,

(5) —(CH2)rC(R1a, R2a)NHCON(R4a, R5a),

(6) —(CH2)rC(R1a, R2a)NHC(═NH)N(R4a, R5a),

(7) —CH(R1a, R2a),

(8) —C≡CH,

(9) —(CH2)rC(R1a, R2a)CN, and

(10) —(CH2)rC(R1a, R2a)CO2R3a,

wherein R1a, R2a, R2a, R4a, and R5a, are independently selected from the group consisting of

(a) H,

(b) substituted or unsubstituted C1-C6-alkyl,

(c) C1-C6-alkyl substituted with aryl,

(d) C1-C6-alkyl substituted with heterocyclyl, and

(e) C1-C6-alkyl substituted with heteroaryl,

or R4a and R5a, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S;

r is an integer of 0-4;

Q is absent or selected from the group consisting of

(1) —C(═O)N(R1, R2),

(2) —NHC(═O)N(R1, R2),

(3) —N(OH)C(═O)N(R1, R2),

(4) —CH(OH)C(═O)N(R1, R2),

(5) —CH[N(R2q, R3q)]C(═O)N(R1, R2), and

(6) —CHR1qC(═O)N(R1, R2),

R1 is selected from the group consisting of

(1) H,

(2) OH,

(3) OC1-6-alkyl,

(4) N(R2q, R3q), and

(5) substituted or unsubstituted C1-6-alkyl;

R2 is selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl,

(5) substituted or unsubstituted heteroaryl,

(6) C1-C6-alkyl substituted with aryl,

(7) C1-C6-alkyl substituted with heterocyclyl, and

(8) C1-C6-alkyl substituted with heteroaryl,

or R1 and R2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,

R1q, R2q, and R3q are selected from H or C1-C6 alkyl,

wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

3. A compound of claim 1, having the formula II:

1482

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together, is selected from the group consisting of

1483 1484 1485 1486 1487

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

X is selected from the group consisting of

(1) —(C═O)—,

(2) —C1-C6-alkyl-(C═O)—, and

(2) —C2-C6-alkenyl-(C═O)—.

4. A compound of claim I, having the formular III:

1488

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together, is selected from the group consisting of

1489 1490 1491 1492 1493

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

X is selected from the groups consisting of

(1) —(C═O)—,

(2) —C1-C6-alkyl-(C═O)—, and

(3) —C2-C6-alkenyl-(C═O)—.

5. A compound of claim 1, having the formula IV:

1494

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together, is selected from the group consisting of

1495 1496 1497 1498 1499

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

X is selected from the groups consisting of

(1) —(C═O)—,

(2) —C1-C6-alkyl-(C═O)—, and

(3) —C2-C6-alkenyl-(C═O)—.

6. A compound of claim 1, having the formula V:

1500

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together, is selected from the group consisting of

1501 1502 1503 1504 1505

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

X is selected from the group consisting of

(1) —(C═O)—,

(2) —C1-C6-alkyl-(C═O)—, and

(3) —C2-C6-alkenyl-(C═O)—.

7. A compound of claim 1, having the formula VI:

1506

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

E is absent or selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl, and

(5) substituted or unsubstituted heteroaryl,

or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S,

R1L, R3L are independently selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl,

or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

8. A compound of claim 1, having the formula VII:

1507

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

E is absent or selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl, and

(5) substituted or unsubstituted heteroaryl,

or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

R1L, R3L are independently selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl,

or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

9. A compound of claim 1, having the formula VIII:

1508

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

E is absent or selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl, and

(5) substituted or unsubstituted heteroaryl,

or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

R1L, R3L are independently selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl,

or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

10. A compound of claim 1, having the formula IX:

1509

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

E is absent or selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-allkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl, and

(5) substituted or unsubstituted heteroaryl,

or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

R1L, R3L are independently selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl,

or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

11. A compound of claim 1, having the formula X:

1510

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

E is absent or selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl, and

(5) substituted or unsubstituted heteroaryl,

or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S;

R1L, R3L are independently selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl,

or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

12. A compound of claim 1, having the formula XI:

1511

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

Y—X taken together, is selected from the group consisting of

1512 1513

13. A compound of claim 1, having the formula XII:

1514

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

R1b and R2b are independently selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted C2-C6-alkenyl,

(4) substituted or unsubstituted C2-C6-alkenyl,

(5) substituted or unsubstituted aryl,

(6) substituted or unsubstituted heterocyclyl,

(7) substituted or unsubstituted heteroaryl,

(8) C1-C6-alkyl substituted with aryl,

(9) C1-C6-alkyl substituted with heterocyclyl, and

(10) C1-C6-alkyl substituted with heteroaryl;

q is an integer of 0-2;

14. A compound of claim 1, having the formula XIII:

1515

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

R4 is selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl;

A is H or —CH(CH3)OH—;

R1 is H or substituted or unsubstituted C1-6-alkyl;

R2 is selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) substituted or unsubstituted aryl,

(4) substituted or unsubstituted heterocyclyl,

(5) substituted or unsubstituted heteroaryl,

(6) C1-C6-alkyl substituted with aryl,

(7) C1-C6-alkyl substituted with heterocyclyl,

(8) C1-C6-alkyl substituted with heteroaryl,

or R1 and R2 together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

15. A compound of claim 1, having the formula XIV:

1516

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together is selected from the group consisting of

1517 1518 1519 1520 1521

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

R4 is selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl.

16. A compound of claim 1, having the formula XV:

1522

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together, is selected from the group consisting of

1523 1524 1525 1526 1527

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

17. A compound of claim 1, having the formula XVI:

1528

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together, is selected from the group consisting of

1529 1530 1531 1532 1533

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3;

R4 is selected from the group consisting of

(1) H,

(2) substituted or unsubstituted C1-C6-alkyl,

(3) C1-C6-alkyl substituted with aryl,

(4) C1-C6-alkyl substituted with heterocyclyl, and

(5) C1-C6-alkyl substituted with heteroaryl;

18. A compound of claim 1, having the formula XVII:

1534

or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein

D-G-Y taken together, is selected from the group consisting of

1535 1536 1537 1538 1539

wherein

R is selected from the group consisting of —CH3, —C2H5, —CH2OH, —OH, —OCH3, —OC2H5, —OCF3, —CN, —NO2, —CO2H, —CO2CH3, —CONH2, —NH2, —F, —Cl, —Br, —CF3, —N(CH3)2, —NHSO2CH3, and —NHCOCH3.

19. A pharmaceutical composition comprising a compound from one of claims 1-18 and a pharmaceutically acceptable excipient.

20. A pharmaceutical composition comprising a compound from one of claims 1-18, a second agent, and a pharmaceutically acceptable excipient.

21. A method of treating a patient comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 1-18.

22. A method of treating a patient comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 1-18 and an effective amount of a second agent.

23. A method of treating an infection comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 1-18.

24. A method of treating an infection comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 1-18 and an effective amount of a second agent.