Abstract: The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) for treatment of pulmonary conditions (e.g. asthma). The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

Abstract: The instant invention is directed towards tetracycline compositions, and methods of inhibiting Tdp1 activity, and methods of treating Tdp1-associated disorders.

Abstract: This disclosure provides compositions containing solid forms of tazobactam arginine, and methods of manufacturing and using these compositions.

Abstract: This disclosure provides compositions containing solid forms of tazobactam arginine, and methods of manufacturing and using these compositions.

Abstract: Provided are: a radiolabeled drug, which is efficiently accumulated in a target and has high in vivo stability; and diagnosis and treatment each using the radiolabeled drug. Specifically provided are: a radiolabeled drug showing increased accumulation in a target site, which comprises a complex composed of a ligand that is bound to a compound capable of binding to a target molecule and forms a polycoordinated complex with a metal (e.g., technetium or rhenium) and a radionuclide of the metal; the radiolabeled drug for diagnosis or treatment; a ligand for preparing the radiolabeled drug; a kit that comprises a drug comprising the ligand and a drug comprising a radionuclide of a metal, as separate package units; and a method of increasing accumulation of a radiolabeled drug in a target site, comprising using the above-mentioned radiolabeled drug.

Abstract: A compound of formula (I) or formula (Ia) Wherein R1, Ra, R2, X, R3, Y1, Y2, A, B and C are as defined herein. Also, pharmaceutical compositions comprising such compounds and excipients, methods of treating bacterial infections comprising administering such compounds, methods for making such compounds and hydrates of such compounds.

Abstract: Photoactivatable antimicrobial compounds and methods for the use thereof in the treatment of infections are provided.

Abstract: An improved process for the production of lyophilized Piperacillin alone or in combination with Tazobactam with improved pH adjustment, by degassing the solution of products to a controlled low carbon dioxide content prior to lyophilization.

Abstract: The instant invention is directed towards tetracycline compositions, and methods of inhibiting Tdp1 activity, and methods of treating Tdp1-associated disorders.

Abstract: The present invention relates to novel thiosulfonates derivatives. The present invention also provides methods for preventing, treating and/or reducing inflammation-associated diseases in the cardiovascular, connective tissue, pulmonary, gastrointestinal, respiratory, urogenital, nervous or cutaneous systems as well as infective and tumoral diseases employing said compounds.

Abstract: A fullerene-antibiotic conjugate including at least one antibiotic molecule per fullerene moiety. The fullerene may comprise C60 and the antibiotic may comprise vancomycin or may be selected from the group consisting of penicillins, cephalosporins, quinolones, fluoroquinolones, macrolides, lincosamines, carbepenems, conobactams, aminoglycosides, glycopeptides, tetracyclines, sulfonamides, rifampin, oxazolidonones, and streptogramins. The conjugate preferably includes at least two and more preferably at least three antibiotic molecules per C60 center. A method for making a fullerene(C60)-antibiotic conjugate, comprises: synthesizing a linker precursor (I); reacting the linker precursor (I) with C60 via a Bingel-reaction, to produce a fullerene-linker conjugate (II); hydrolyzing the fullerene-linker conjugate (II), resulting in a desired derivative of C60 (III); and reacting the derivative (III) with a desired antibiotic to produce a fullerene-antibiotic conjugate (IV).

Abstract: The present invention is based on the discovery that certain fermentation products of the marine actinomycete strains CNB392 and CNB476 are effective inhibitors of hyperproliferative mammalian cells. The CNB392 and CNB476 strains lie within the family Micromonosporaceae, and the generic epithet Salinospora has been proposed for this obligate marine group. The reaction products produced by this strain are classified as salinosporamides, and are particularly advantageous in treating neoplastic disorders due to their low molecular weight, low IC50 values, high pharmaceutical potency, and selectivity for cancer cells over fungi.

Abstract: Catacholate beta-lactam conjugates, methods for producing these compounds, and compositions containing these compounds useful as siderophores or for treatment of bacterial infections are provided.

Abstract: The present invention provides substituted amino bicyclic-&bgr;-lactam penam derivatives and substituted amino bicyclic-&bgr;-lactam cepham derivatives and their diastereoisomers of formula I, as well as compositions, methods of making, and methods of using, which exhibit excellent cysteine protease inhibitory activity and which may be used for treatment of different diseases such as cancer (including cancer metastasis), osteoporosis, rheumatoid arthritis.

Abstract: The present invention is directed compositions of the formula: ##STR1## wherein: D is a residue of a biologically active moiety;X is an electron withdrawing group;Y and Y' are independently O or S;(n) is zero (0) or a positive integer, preferably from 1 to about 12;R.sub.1 and R.sub.2 are independently selected from the group consisting of H, C.sub.1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls and substituted C.sub.1-6 alkyls;R.sub.3 is a substantially non-antigenic polymer, C.sub.1-12 straight or branched alkyl or substituted alkyl, C.sub.5-8 cycloalkyl or substituted cycloalkyl, carboxyalkyl, carboalkoxy alkyl, dialkylaminoalkyl, phenylalkyl, phenylaryl or ##STR2## R.sub.4 and R.sub.5 are independently selected from the group consisting of H, C.sub.1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls, and substituted C.sub.1-6 alkyls or jointly form a cyclic C.sub.5 -C.sub.7 ring.

Abstract: A process to prepare the E isomer of a 3-substituted (6R,7R)-7-phenyl-acetamido-ceph-3-em-4-carboxylic acid from a mixture of the E and Z-isomer of either the corresponding tert-butyl or the corresponding 4-methoxybenzyl ester of a 3-substituted (6R,7R)-7-phenylacetamido-ceph-3-em-4-carboxylate, characterized by the application of a compound selected from the group titanium tetrachloride, tin tetrachloride and tellurium tetrachloride.

Abstract: Pharmaceutical compositions with heretofore unknown and enhanced physical, chemical, and biological properties are prepared by combining known biologically active parent compounds with oxo thia azabicyclo compounds, such as lactam and .beta.-lactam compounds, capable of rapidly transporting the parent compounds in undegraded form to their target sites of action. A process for combining the parent compound with .beta.-lactam compounds consists of dissolving the parent compound in a polar solvent, adding a .beta.-lactam compound, incubating the resulting mixture, followed by drying, and subjecting the remaining solid material to solvent washing or extraction to further purify the new pharmaceutical composition. The new pharmaceutical composition possesses the biological and therapeutic activity of the parent compound and the barrier penetrating characteristics of the .beta.

Abstract: New solvates of penicillin, in particular amoxycillin glycolate has been provided for together with a simple one-step process to prepare the same.

Abstract: An efficient process for de-esterification has been provided for by application of special tetrahalogenides. By applying this process a new compound, viz. cefesone, and especially the E-isomer thereof, has been prepared.

Abstract: Novel chemotherapeutic agents having utility in treating infectious diseases such as periodontal disease, certain urinary tract infections, and infectious urinary tract stones, are obtained by combining chemically a diphosphonate compound with a therapeutic agent effective against the foregoing diseases.

Abstract: Novel chemotherapeutic agents having utility in treating infectious diseases such as periodontal disease, certain urinary tract infections, infectious urinary tract stones, and bone cancer, are obtained by combining chemically a diphosphonate compound with a therapeutic agent effective against the foregoing diseases.

Abstract: Method of desilylating a silylether compound by reacting a silylether compound of the general formula (I): ##STR1## or a salt thereof with an amine hydrogen fluoride salt or a pyridine hydrogen fluoride salt in an organic solvent to produce a compound of the general formula (IV): ##STR2## According to this method, silylether compounds that are labile under strong acidic or basic conditions can be desilylated efficiently using inexpensive reagents.

Abstract: The present invention provides processes for making compounds of the structure(Q--L.sup.1)--L--(L.sup.2 --B)wherein(I) Q is a quinolone moiety;(II) B is a lactam moiety; and(III) L, L.sup.1, and L.sup.2 together comprise a linking moiety;comprising the steps of:(1) coupling a compound of Formula (III) with a lactam-containing compound to form an intermediate compound; and(2) cyclizing the intermediate by reaction with an organosilicon compound to give a compound of the formula (Q--L.sup.1)--L--(L.sup.2 --B).Preferably, the process additionally comprises a step prior to the coupling step, wherein protected forms of the compound of Formula (III) and the lactam compound are formed; and deprotection steps after the cyclization step, wherein the protecting groups are removed. Preferred antimicrobial compounds made by these processes are those where the beta-lactam moiety is a penem, a carbapenem, a cephem, or a carbacephem. Also preferred are those compounds where L.sup.1, L, and L.sup.

Abstract: The present invention discloses compounds having the formula ##STR1## wherein one of R.sup.1 and R.sup.2 is --COR.sup.4, --CN, --CH.sub.2 R.sup.5, halogen, --CH.dbd.CHR.sup.6 or Q and the other is hydrogen or lower alkyl or both R.sup.1 and R.sup.2 together form a .gamma.-lactam ring,R.sup.3 is hydrogen, lower alkyl, aryl-alkyl, allyl or a residue which is cleavable in vivo,R.sup.4 is hydrogen, lower alkyl, lower alkoxy, benzyloxy, amino, lower alkylamino or lower alkyl-lower alkoxyamino,R.sup.5 is hydroxy, --OCONHR.sup.7, --OCONH.sub.2 or a five- or six-membered hetero-aromatic ring which contains N,S and/or O and which is linked via a nitrogen atom,R.sup.6 is --CN or CHO,R.sup.7 is --COCH.sub.2 Cl,Q is a five- or six-membered hetero-aromatic ring which contains N, S and/or O andn is 0, 1 or 2,and the pharmaceutically compatible salts thereof.These compounds are good .beta.-lactamase inhibitors. They can be used for the prevention or treatment of bacterial infections, optionally together with a .beta.

Abstract: Compounds of structure: ##STR1## as well as their pharmaceutically-acceptable salts and biohydrolyzables esters, and hydrates thereof, are effective antiinfective agents, useful in treating and preventing infection.

Abstract: Conjugates of general formula 1:[A--O--W--Z].sub.a --T 1wherein the moiety A--O-- is the residue of drug of formula A--O--H in which --O--H is a primary or secondary hydroxyl group; a is an integer of from 1 to 30; W is a group of general formula 2: ##STR1## wherein b is an integer of from 1 to 4, B represents a C.sub.1 -C.sub.3 alkylene group and R.sub.1 and R.sub.2 each independently represent hydrogen, halogen, alkyl, phenyl or substituted phenyl; Z is a spacer group and T is a carrier moiety.

Abstract: The present invention is related to compounds which inhibit pancreatic cholesterol esterase. The compounds have the formula: ##STR1## wherein R.sup.1 is H or C.sub.1-6 alkyl;R.sup.2 is H or C.sub.1-6 alkyl;R.sup.3 is H or C.sub.1-6 alkyl;X is CHR.sup.6, S or O;R.sup.6 is H or C.sub.1-6 alkyl;R.sup.4 is a hydrophobic moiety; and pharmaceutically acceptable salts thereof.

Abstract: Conjugate of general formula 1:[A--O--W-Z].sub.a -T 1wherein the moity A--O--is the residue of drug of formula A--O--H in which --O--H is a primary or secondary hydroxyl group; a is an integer of from 1 to 30; W is a group of general formula 2: ##STR1## wherein b is an integer of from 1 to 4, B represents a C.sub.1 -C.sub.3 alkylene group and R.sub.1 and R.sub.2 each independently represent hydrogen, halogen, alkyl, phenyl or substituted phenyl; Z is a spacer group and T is a carrier moiety.

Abstract: A penam derivative represented by the following general formula or a salt thereof: ##STR1## wherein R.sup.1 represents a hydrogen atom, an amino-protecting group or an acyl group; R.sup.2 represents a hydrogen atom or a lower alkyl group; R.sup.3 represents a hydrogen atom, a lower alkoxy group, a lower alkylthio group or a formamido group; R.sup.4 represents an protected or unprotected carboxyl group or a carboxylato group; R represents a group of the formula, --NHR.sup.5 or --NR.sup.5 R.sup.6 (in which R.sup.5 and R.sup.6, which may be the same or different, represent protected or unprotected hydroxyl groups, cyano groups, sulfo groups, or unsubstituted or substituted lower alkyl, aryl, acyl, carbamoyl, sulfamoyl, lower alkylsulfonyl or heterocyclic groups) or a group of the formula, --N.dbd.CR.sup.7 R.sup.8 (in which R.sup.7 and R.sup.

Abstract: The present invention provides methods of making compounds of the structure[Q-L.sup.1 ]-L-[L.sup.2 -B[wherein(I) Q is a quinolone moiety;(II) B is a beta-lactam moiety;(III) L, L.sup.1, and L.sup.2 together comprise a carbamate-containing linking moietycomprising the steps of:(1) Reacting a lactam compound of the formula B-L.sup.4 -H with phosgene to form an intermediate compound of the formula B--L.sup.4 --C(=O)--Cl, where L.sup.4 is oxygen; and(2) Coupling said intermediate compound with a quinolone compound of the formula Q-L.sup.3 -R.sup.44 ; wherein L.sup.3 is nitrogen; R.sup.44 is hydrogen, Si(R.sup.45).sub.3, or Sn(R.sup.45).sub.3 ; and R.sup.45 is lower alkyl.Preferably, the process additionally comprises steps prior to the reacting and coupling steps where esters of the lactam and quinolone compounds are made. Also preferably, the coupling step comprises adding a solution containing the quinolone compound to a solution containing the intermediate compound.

Abstract: A penam derivative represented by the following general formula or a salt thereof: ##STR1## wherein R.sup.1 represents a hydrogen atom, an amino-protecting group or an acyl group; R.sup.2 represents a hydrogen atom or a lower alkyl group; R.sup.3 represents a hydrogen atom, a lower alkoxy group, a lower alkylthio group or a formamido group; R.sup.4 represents a protected or unprotected carboxy group or a craboxylato group; R represents a group of the formula, --NHR.sup.5 or --NR.sup.5 R.sup.6 (in which R.sup.5 and R.sup.6, which may be the same or different, represent protected or unprotected hydroxyl groups, cyano groups, sulfo groups, or unsubstituted or substituted lower alkyl, aryl, acyl, carbamoyl, sulfamoyl, lower alkylsulfonyl or heterocyclic groups) or a group of the formula, --N.dbd.CR.sup.7 R.sup.8 (in which R.sup.7 and R.sup.

Abstract: Novel beta lactam compounds having potent elastrase inhibition activity are disclosed. These compounds are characterized by the general structural formulae I, II, and III: ##STR1## These compounds are further characterized such that X and Y are each --S-- or --CH.sub.2 --, with at least one of X and Y being --S--, or alternatively, X is --SO-- or --SO.sub.2 -- and Y is --CH.sub.2 --; R.sup.1 is hydrogen, tri(lower alkyl)silyl, --COOR" or --CONHR"', wherein R" and R"' are each lower alkyl or phenyl(lower alkyl), and may be the same or different; R.sup.3 is hydrogen, lower alkyl or (lower alkyl)oxy; one of B and D is (lower alkyl)oxycarbonyl, (lower alkenyl)oxycarbonyl, allyloxycarbonyl or phenyl(lower alkyl)oxycarbonyl; and the other of B and D is hydrogen or lower alkyl.The compounds are useful as anti-inflammatory agents, particularly in the treatment of adult respiratory distress syndrome and rheumatoid arthritis.

Abstract: There is disclosed a compound represented by the formula ##STR1## where P is a hydroxy protecting group.

Abstract: The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are:(a) compounds of the formula[D-DHC] (I)wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine.revreaction.pyridinium salt redox carrier, with the proviso that when [DHC] is ##STR1## wherein R is a lower alkyl or benzyl and [D] is a drug species containing a single NH.sub.2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH.sub.

Abstract: Disclosed is a process for preparing 2.beta.-substituted-methylpenicillin derivative of the formula ##STR1## wherein R is H or carboxyl protecting group, R.sub.1 is H or halo, R.sub.2 is H, lower alkyl, lower alkoxy, halogen, azido, lower alkylthio, phthalimide or a group --NHR.sub.3 (wherein R.sub.3 is H or acyl), and --N Y is an optionally substituted monocyclic or bicyclic heterocyclic group having 1 to 4 nitrogen atoms in the ring structure, the process comprising reacting a compound of the formula ##STR2## wherein X is Cl or Br, and R, R.sub.1 and R.sub.2 are as defined above with a heterocyclic compound of the formula ##STR3## wherein --N Y is as defined above.

Abstract: .beta.-Lactam antibiotics having an .alpha.-formamido substituent on the carbon atom adjacent to the carbonyl group of the .beta.-lactam ring and in particular bicyclic compounds having the partial structure: ##STR1## Intermediates and processes for the preparation of the compounds are further disclosed.

Abstract: Disclosed is a penicillin derivative of the formula: ##STR1## wherein n is an integer of 0, 1 or 2; Y is a cyano group, a lower acyl group, a mono- or di-lower alkylthiocarbamoyl group, ##STR2## wherein R.sub.1 is a hydrogen atom, a lower alkyl group, a phenyl group, a group --(CH.sub.2).sub.m --OR.sub.2 or --(CH.sub.2).sub.m COOR.sub.2 (m is an integer of 1 to 6 and R.sub.2 is a hydrogen atom or a penicillin carboxyl ester-forming group which is commonly used for penicillin derivatives) or a phenyl group substituted by at least one member selected from the class consisting of lower alkyl group, halogen atom and lower alkoxy group; and R is a hydrogen atom or a penicillin carboxyl ester-forming group, or a salt thereof. They are useful as .beta.-lactamase inhibitors.

Abstract: A multi-step stereospecific process for preparing (3S,4R,5R)-1-(allyloxycarbonyl)-methyl-3-(1-hydroxyethyl)-4-beta-naphthoxy thiocarbonylthio-2-azetidinones, stereoisomers thereof or hydroxy protected analogs thereof from anhydropenicillin. The azetidinones are intermediates useful for producing penems which are a known group of antibacterial compounds. The process involves protecting the hydroxy group of anhydropenicillin with a readily removable hydroxy protecting group, then converting the resulting compound by ozonolysis followed by reaction with a trialklyl phosphite, then hydrolysis to remove the methylidene group at the 2-position of anhydropenicillin. The resulting compound is converted to the unprotected 4-beta-naphthoxy thiocarbonylthio derivative by reaction with allyl alcohol and HCl followed by reaction with O-2-napththalenylcarbonochloridothioate, or to the protected compound by reaction with silver imidazolate and allyl alcohol followed by reaction with O-2-naphthalenylcarbonochloridothioate.

Abstract: 6-(1-Acyl-1-hydroxymethyl)penicillanic acid derivatives are useful as antibacterials and/or beta-lactamase inhibitors.

Abstract: This invention provides a penicillin derivative of the formula ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and represent hydrogen, C.sub.1-6 alkyl, C.sub.1-6 hydroxyalkyl, C.sub.3-9 acyloxyalkyl, C.sub.8-13 benzyloxyalkyl, C.sub.2-7 alkoxyalkyl, C.sub.2-7 alkoxycarbonyl, C.sub.3-8 alkenyloxycarbonyl, C.sub.3-8 alkynyloxycarbonyl, phenyl, amino, cyano, formyl, trifluoromethyl, C.sub.2-6 acyl, carbamoyl, C.sub.2-7 alkylcarbamoyl, benzyloxycarbonylamino, C.sub.2-7 alkoxycarbonylamino; and R.sub.3 is hydrogen, a group for forming a pharmaceutically acceptable salt, or a penicillin carboxyl protecting group, with the proviso that both of R.sub.1 and R.sub.2 are not hydrogen or C.sub.2-7 alkoxycarbonyl at the same time and that when one of R.sub.1 and R.sub.2 is hydrogen, the other is not C.sub.2-7 alkoxycarbonyl, or a pharmaceutically acceptable acid addition salt, process for preparing the derivative, and a pharmaceutical composition containing the derivative.

Abstract: Described is a novel process for the preparation of penams and penems useful as antibacterial agents, which comprises the reaction of an appropriate 4-substituted-azetidin-2-one with a base, followed by reaction of the thereby formed penam compound with an oxidating agent and a organic or inorganic base.Also described are novel penam compounds useful as antibacterials which are prepared by the described process.

Abstract: The (5-R-2-oxo-1,3-dioxolen-4-yl)methyl moiety: ##STR1## wherein R is loweralkyl of 1-6 carbon atoms, especially methyl or t-butyl; when utilized as an ester on a pharmaceutical having a carboxylic acid functionality, enhances oral absorption of the pharmaceutical. This effect is applicable to a broad range of pharmaceutically active substances, including antibiotics, and antihypertensives as well as other classes of therapeutic agents.

Abstract: A novel stereocontrolled process is disclosed for converting 6-aminopenicillanic acid to an optically active azetidinone of the formula ##STR1## wherein R" is a hydroxy-protecting group by use of a 6,6-dihaloanhydropenicillin or 6,6-bis(phenylselenyl)anhydropenicillin intermediate.