Abstract: The instant invention provides a process for the selective N-formylation of N-hydroxylamines.

Abstract: The invention concerns compounds of general formula (X) in which Y represents in particular —CONHOH, R1 represents in particular a C1-C5 alkyl group, AA represents an amino acid, or an amino acid sequence, and R3 represents in particular a group of formula —NH—(CH2)2—SCH3. The invention also concerns the pharmaceutical compositions containing them, and the methods for obtaining them.

Abstract: Matrix metalloproteinases (MMps) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.

Abstract: Compounds having the formula 1

Abstract: The instant invention provides a process for the selective N-formylation of N-hydroxylamines.

Abstract: A compound of formula (I) wherein X is a —CONHOH group and the R groups are defined in the claims. The compounds are inhibitors of matrix metalloproteinases involved in tissue degradation and inhibitors of the release of tumour necrosis factor from cells.

Abstract: The invention discloses hydroxamide acids of the formula: which are useful in treating disease conditions mediated by TNF-&agr;, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

Abstract: The present invention relates to therapeutically active hydroxamic acid, N-formyl-N-hydroxyamino and carboxylic acid derivatives, their preparation, and pharmaceutical compositions containing them. These compounds are useful in the inhibition of metalloproteases, such as stromelysin, gelatinase, matrilysin, and collagenase. These compounds are useful in the treatment of mammals having disease-states alleviated by the inhibition of such matrix metalloproteases.

Abstract: This invention relates to compounds of general formula (I): in which Ar is a group selected from: A1, A2, B, C, D, E, Q1-Q3, R1-R9, Z1 and Z2 are as defined in the disclosure, and Y represents carboxy or an acid bioisostere. These compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.

Abstract: A method is provided for the transition metal-catalyzed arylation, or vinylation, of hydrazines, hydrazones, and the like. Additionally, the invention provides a conceptually novel strategy, the cornerstone of which is the transition metal-catalyzed arylation or vinylation method, for the synthesis of indoles, carbazoles, and the like. The methods and strategies of the invention may be utilized in standard, parallel, and combinatorial synthetic protocols.

Abstract: The subject invention involves processes for making hydroxamic acid compounds using a solid-support resin having an oxime moiety as the linking moiety of the resin, comprising the steps of (a) treating the resin with a carboxylic acid compound, such that it is attached to the resin by a condensation reaction between the oxime and carboxyl moieties; (b) optionally modifying the side chain; (c) cleaving a product from the resin by treating with O-tert-butyldimethylsilylhydroxylamine; (d) optionally modifying the side chain; and (e) optionally treating the resulting O-TBS-protected material with acid to produce an unprotected hydroxamic acid compound.

Abstract: Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula (T)xA—B—D—E—G wherein A is an aryl or heteroaryl rings; B is an aryl or heteroaryl ring or a bond; each T is a substituent group; x is 0, 1, or 2; the group D represents the group E represents a two or three carbon chain bearing one to three substituent groups which are independent or are involved in ring formation, possible structures being shown in the text and claims; and the group G represents and with the proviso that when G is each of the substituents on E is an independent substituent; and include pharmaceutically acceptable salts thereof.

Abstract: Compounds of the formula (I) where X is a —CO2H or —CONHOH group; Y and Z are independently sulphur or oxygen, at least one being sulphur; R1 is hydrogen, hydroxy, (C1-C6)alkyl, (C2-C6)alkenyl, or (C3-C8cycloalkyl; R2 is a (C1-C24)alkyl, phenyl(C1-C6)alkyl, or phenyl(C0-C6alkyl)O)C1-C6)alkyl, any of which may be optionally substituted by (C1-C6)alkyl, (C1-C6)alkoxy, halo or cyano (CN); R3 is the characterising side chain of a natural &agr;-amino acid in which any functional groups may be protected, (C1-C6)alkyl which may be optionally substituted, or cycloalkyl(C1-C6)alkyl; R4 is hydrogen, (C1-C6)alkyl, phenyl(C1-C6)alkyl, optionally substituted phenyl or heteroaryl, or a group of formula —(Q—O)n—Q where Q is a straight or branched (C1-C6)alkyl, where n is an integer >1 and no continuous linear sequence of atoms in the group R4 is >12; or a salt, hydrate or solvate thereof.

Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof. Such compounds may be incorporated into pharmaceutical compositions which can inhibit various enzymes from the matrix metalloproteinase family.

Abstract: Compounds having the formula are matrix metalloproteinase inhibitors. Also disclosed are matrix metalloproteinase-inhibiting compositions and methods of inhibiting matrix metalloproteinase in a mammal.

Abstract: Compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, AA and Y are as defined herein, inhibit phosphodiesterase type IV or inhibit the production of tumor necrosis factor, and therefore are useful in the treatment of certain conditions and diseases including asthma, arthritis, and sepsis.

Abstract: A family of compounds having the general structural formula where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof.

Abstract: Compounds of formula (I) are useful as therapeutic agents, by virtue of having MMP and TNF inhibitory activity.

Abstract: A silver halide photographic material is disclosed, comprising a support having thereon at least one light-sensitive silver halide emulsion layer, wherein said silver halide photographic material contains a compound by formula (IA), or which contains at least one hydroxamic acid compound having a bicyclo ring as a partial structure and represented by formula (IB).

Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.

Abstract: A family of compounds having the general structural formula where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof. Also described are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine.

Abstract: New compounds of the general formula (I) ##STR1## (wherein R.sup.1 is a hydrogen atom, or a hydroxyl, aryl (C.sub.1 -C.sub.6)alkylene or --A--SOn--B group (A is a (C.sub.1 -C.sub.6) alkylene group; B is a (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) acyl, aryl or heterocyclyl group; n is 0, 1 or 2), R.sup.2 is a hydrogen atom, or a (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) alkyloxy 10 or (C.sub.1 -C.sub.6) alkylthio group, R.sup.3 and R.sup.4 are identical or different, representing a hydrogen atom, or a (C.sub.1 -C.sub.6) alkyl, aryl or aryl(C.sub.1 -C.sub.6)alkylene group, R.sup.5 is a --Y--C or C group (Y is a (C.sub.1 -C.sub.6) alkylene group, an oxygen atom, an imino group or a (C.sub.1 -C.sub.6) alkyleneimino group, C is a sulfonic acid, phosphonic acid, amidino, (C.sub.1 -C.sub.6) acyl, acylimidoyl, diphosphonomethine or dicarboxymethine group), and R.sup.

Abstract: Compounds of general formula (I) ##STR1## wherein X ia a --CO.sub.2 H, --NH(OH)CHO or --CONHOH group; R.sub.1 is a cylcoalkyl, cycloalkenyl or non-aromatic heterocyclic ring containing up to 3 heteroatoms, any of which may be (i) substituted by one ore more substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, halo, cyano (--CN), --CO.sub.2 H, --CO.sub.2 R, --CONH.sub.2, --CONHR, --CON(R).sub.2, --OH, --OR, oxo-, --SH, --SR, --NHCOR, and --NHCO.sub.2 R wherein R is C.sub.1 -C.sub.6 alkyl or benzyl and/or (ii) fused to a cycloalky or heterocyclic ring; and R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are as defined in specification are matrix metalloproteinase inhibitors.

Abstract: The present invention relates to a TEMPO-catalyzed oxidation of primary alcohols, RCH.sub.2 OH to corresponding carboxylic acids, RCOOH in the presence of catalytic in the presence of catalytic amount of NaClO and stoichiometric amount of NaClO.sub.2 as an oxidant.

Abstract: A silver halide photographic material is disclosed, comprising a support having thereon at least one light-sensitive silver halide emulsion layer, wherein said silver halide photographic material contains a compound by formula (IA), or which contains at least one hydroxamic acid compound having a bicyclo ring as a partial structure and represented by formula (IB).

Abstract: The invention provides novel PGF analogs. In particular, the present invention relates to compounds having a structure according to the following formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X, Y, and Z are defined below. This invention also includes optical isomers, diastereomers and enantiomers of the formula above, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof.The compounds of the present invention are useful for the treatment of a variety of diseases and conditions, such as bone disorders and glaucoma. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment for bone disorders and glaucoma using theses compounds or the compositions containing them.

Abstract: Compounds of formula (I): ##STR1## where the substituents are as defined herein, and salts thereof, are matrix metalloprotease inhibitors.

Abstract: This invention is directed to compounds of formula I: ##STR1## wherein the variables are as described herein. Compounds within the scope of the present invention possess useful properties, more particularly pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase.

Abstract: A sulfur-containing amino acid compound having a high inhibitory activity on LTA.sub.4 hydrolase which is represented by the following formula: ##STR1## wherein R.sup.1 represents H, alkyl, optionally substituted phenyl alkyl, alkanoyl or optionally substituted benzoyl; R.sup.2 represents ester, amide or carboxyl; R.sup.3 represents hydroxyl, alkyl, halogenoalkyl, alkoxy, halogenoalkoxy, alkylthio, optionally substituted phenyl, optionally substituted phenoxy, optionally substituted phenylthio, halogen atom, alkylsulfonyl, halogenoalkylsulfonyl, nitro or cyano; R.sup.4 represents alkyl; A.sup.1 represents alkylene; and A.sup.2 represents alkylene.

Abstract: Compounds of general formula (II), wherein X is a hydroxamic or carboxylic acid group, Y is sulphonyl and R.sub.1 and R.sub.2 as defined in the claims are matrix metalloproteinase inhibitors.

Abstract: Compounds of formula (I) wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X are as defined in the specification and are prepared by elimination of one of the groups X.sub.1 and X.sub.2 from a compound of formula (II) wherein X.sub.1 and X.sub.2 each independently represent a carboxylic acid group or salt thereof, or a protected carboxylic acid group, the non-eliminated group X.sub.1 or X.sub.2 corresponding to the group X in the desired compound of formula (I).

Abstract: Iminooxymethyleneanilides of the formula I ##STR1## where the substituents and the index have the following meanings: R is hydrogen,unsubst. or subst. alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkylcarbonyl or alkoxycarbonyl;R.sup.1 is alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl and in the case where X is NR.sup.a, additionally hydrogen;X is a direct bond, O or NR.sup.a ;R.sup.a is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl;R.sup.2 is cyano, nitro, trifluoromethyl, halogen, alkyl or alkoxy;n is 0, 1 or 2;R.sup.3 is hydrogen, hydroxyl, cyano, cyclopropyl, trifluoromethyl, halogen, alkyl, alkoxy or alkylthio;R.sup.4 is hydrogen, hydroxyl, halogen, alkyl, haloalkyl, alkoxy, alkylthio,unsubstituted or substituted cycloalkyl, heterocyclyl, aryl, arylalkyl, hetaryl or hetarylalkyl;R.sup.

Abstract: The present invention relates to the discovery of novel, low molecular weight, non-peptide inhibitors of matrix metalloproteinases (e.g. gelatinases, stromelysins and collagenases) and TNF-.alpha. converting enzyme (TACE, tumor necrosis factor-.alpha.

Abstract: The invention is directed to therapeutically active hydroxamic acid derivatives of formula (I): ##STR1## wherein the substituents are as defined in the specification. These therapeutically active hydroxamic acid derivatives have high intrinsic activity against a broad spectrum of matrix metalloproteinases (MMPs), good oral bioavailability, and additionally inhibit tissue necrosis factor (TNF) production.

Abstract: Compounds of general Formula I: ##STR1## are presented which have collagenase inhibition activity and are useful in the management of disease involving tissue degradation and the promotion of wound healing. Representative diseases involving include arthropathy (particularly rheumatoid arthritis), inflammation, dermatological diseases, bone resorption disease and tumor invasion.

Abstract: Synthetic mammalian matrix metalloprotease inhibitors are disclosed that are useful for treating or preventing diseases wherein said diseases are caused by unwanted mammalian matrix metalloprotease activity and include skin disorders, keratoconus, restenosis, rheumatoid arthritis, wounds, cancer, angiogenesis and shock.

Abstract: Methods of use for compounds of formula (I) are described wherein R represent a --CONHOH, carboxyl (--CO.sub.2 H) or esterified carboxyl group; R.sup.1 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, aryl, aralkyl, heteroaralkyl or heteroarylthioalkyl group; R.sup.2 represents an optionally substituted phenylethyl, phenylpropyl or phenylbutyl group; R.sup.3 represents a hydrogen atom or an alkyl group; R.sup.4 represents a hydrogen atom or an alkyl group; R.sup.5 represents an optionally substituted alkyl or alkenyl group optionally interrupted by one or more --O-- or --S-- atoms or --N(R.sup.7)-- groups (where R.sup.7 is a hydrogen atom or a C.sub.1-6 alkyl group); X represents an amino (--NH.sub.2), or substituted amino, hydroxyl or substituted hydroxyl group; and the salts, solvates and hydrates thereof.

Abstract: A compound of the formula ##STR1## wherein R.sup.1 is hydrogen, lower alkyl, phenyl-lower alkyl, lower alkanoyl or benzoyl, and each phenyl in the phenyl-lower alkyl and the benzoyl is unsubstituted or substituted by halogen, lower alkyl or alkoxy; R.sup.2 represents a carboxyl or a carboxyl which is converted into an ester, an amide or a hydroxamic acid; R.sup.3 represent a lower alkyl; R.sup.4 represents a lower alkyl; A.sup.1 represents a lower alkylene which is unsubstituted or substituted by a phenyl and the phenyl is unsubstituted or substituted by halogen, lower alkyl or a lower alkoxy; A.sup.2 represents a lower alkylene; A.sup.3 represents a lower alkylene; and Z represents a sulfur or an oxygen. The compounds have inhibitory effects on LTA.sub.4 hydrolase and are useful for treating rheumatic diseases, psoriasis, inflammatory intestinal diseases, gout and cystic fibrosis.

Abstract: Compounds of general formula (I), principally characterized in that R4 is a polyether group, are water soluble matrix metalloproteinase inhibitors.

Abstract: The present invention relates to therapeutically active hydroxamic acid derivatives, to pharmaceutical compositions containing them, and to the therapeutic use of these compounds. In particular, the compounds are inhibitors of matrix metalloproteinases that are involved in tissue degradation, and in addition, are inhibitors of the release of tumor necrosis factor from cells.

Abstract: A method for the preparation of a compound of formula (I) ##STR1## wherein X is hydrogen; Y is (i) a group --CO.sub.2 R.sub.5 wherein R.sub.5 is a carboxyl protecting group or (ii) a group --CONR.sub.6 OR.sub.7 wherein R.sub.6 is an amino protecting group and R.sub.7 is a hydroxyl protecting group; and S.sub.1, S.sub.2, S.sub.3 and S.sub.4 each represent covalently bound moieties which are substantially non-reactive with the reaction components (II), (III), or (IV) defined below, which method comprises causing the co-condensation in a liquid organic medium of a carboxylic acid reaction component of formula (II); an aldehyde of formula (IIIA); ammonia; and an isonitrile reaction component of formula (IV): ##STR2## wherein Y, S.sub.1, S.sub.2, S.sub.3 and S.sub.4 are as defined with respect to formula (I).

Abstract: The present invention provides a compound of formula I ##STR1## or pharmaceutical acceptable salts thereof wherein R.sub.1 is C.sub.4-12 alkyl, C.sub.4-12 alkenyl, C.sub.4-12 alkynyl, --(CH.sub.2).sub.h -C.sub.3-8 cycloalkyl, --(CH.sub.2).sub.h -aryl, or --(CH.sub.2).sub.h -het; R.sub.2 is C.sub.1-12 alkyl, C.sub.2-12 alkenyl, C.sub.2-12 alkynyl, --(CH.sub.2).sub.h -C.sub.3-8 cycloalkyl, --(CH.sub.2).sub.h -C.sub.3-8 cycloalkenyl, --(CH.sub.2).sub.h -aryl, --(CH.sub.2).sub.h -het, --(CH.sub.2).sub.h -Q, --(CH.sub.2).sub.i -X-R.sub.4, or --(CH.sub.2).sub.i CHR.sub.5 R.sub.6. The compounds are inhibitors of matrix metalloproteinases involved in tissue degradation.

Abstract: Compound of formula (I) ##STR1## wherein Ar represents an optionally substituted phenyl or heteroaryl group, m is 1 or 2, n is 0, 1, 2, 3 or 4, X represents --COOH or --CONHOH and R.sub.1, R.sub.3 and Y are as defined in the specification,are inhibitors of metalloproteinases involved in tissue degradation.

Abstract: A silver halide photographic material is disclosed, which comprises a support having thereon at least one light-sensitive silver halide emulsion layer; the silver halide photographic material contains at least one compound represented by the following formula (II), the variables of which are defined in the specification: ##STR1##

Abstract: Compounds of formula (1) are described, wherein R.sup.1 represents (a), where R.sup.3 is a hydrogen or halogen atom or a methyl, trifluoromethyl or methoxy group; R.sup.2 represents a hydrogen atom or a methyl group; and the salts, solvates, hydrates and prodrugs thereof. The compounds are potent and selective orally active inhibitors of the metalloproteinase gelatinase with a long duration of action, and in particular inhibit angiogenesis in vivo. They can therefore be expected to be of use in the prophylaxis or treatment of angiogenesis dependent disorders such as solid tumours and arthritic diseases.

Abstract: A compound of formula (I): ##STR1## wherein: R.sup.1 represents a (C.sub.1 -C.sub.6)alkyl, phenyl, substituted phenyl, or heterocyclyl group; R.sup.2 represents a (C.sub.1 -C.sub.6)alkyl group; R.sup.3 represents:(I) the side chain of arginine, lysine, tryptophan, histidine, serine, threonine, or cysteine, in which any polar amino, hydroxy, mercapto, guanidyl, imidazolyl or indolyl group is rendered substantially non-polar by substitution at the polar N-, O- or S-atom; or(ii) the side chain of aspartic or glutamic acid, in which side chain the carboxylic acid group is amidated;R.sup.4 represents hydrogen or a (C.sub.1 -C.sub.6)alkyl or phenyl (C.sub.1 -C.sub.6)alkyl group; R.sup.5 represents hydrogen or and n is 0, 1 or 2; or substituted phenyl groups; or a salt solvate or hydrate thereof. Compositions containing compound (I) and methods for treatment of diseases or conditions mediated by TNF or MMPs in mammals.

Abstract: Disubstituted tetrahydrofurans, tetrahydrothiophenes, pyrrolidines and cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i. e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase.A method to treat disorders mediated by PAF and/or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

Abstract: The invention relates to compounds of the formula ##STR1## and to pharmaceutically acceptable salts thereof, wherein R.sup.1 is hydrogen, fluoro, or chloro, and R.sup.2 is hydrogen or methyl. The above compounds are lipoxygenase inhibitors. The invention also relates to pharmaceutical compositions containing the above compounds, and to methods of treating inflammatory and allergic conditions by administering the above compounds.

Abstract: The present invention discloses a method comprising the steps of;a) forming in an aqueous solution a hydroxamic acid from a hydroxylamine free base and anhydride having the formula (RCO).sub.2 O wherein R is H or a substituted or unsubstituted C.sub.2-6 alkyl, C.sub.2-6 alkenyl, C.sub.6-10 aryl, or C.sub.4-10 heteroaryl; andb) treating said hydroxamic acid with an alkylating agent in the presence of at least one proton scavenger under conditions sufficient to consume substantially all of said alkylating agent to form an O-substituted hydroxamate.The protection and alkylation are readily effected in water (with no alcohol co-solvent) without the need for phase-transfer catalysis and with little hydrolysis of the alkylating agent.

Abstract: Particularly the invention relates to the compounds of formula I ##STR1## wherein Ar represents carbocyclic aryl, heterocyclic aryl or biaryl;R.sub.1 represents lower alkyl, cycloalkyl, aryl-lower alkyl, lower alkoxy-lower alkyl, aryl, cycloalkyl-lower alkyl, halo-lower alkyl;R.sub.2 represents hydrogen or lower alkyl;R.sub.3 and R.sub.4 represent independently hydrogen, lower alkyl, lower alkoxy, halo, hydroxy, acyloxy, lower alkoxy-lower alkoxy, trifluoromethyl or cyano; or R.sub.3 and R.sub.4 together represent lower allylenedioxy;n represents an integer from 1 to 5;pharmaceutically acceptable prodrug derivatives; and pharmaceutically acceptable salts thereof; methods for preparation thereof;pharmaceutical compositions comprising said compounds; and a method of inhibiting TNF-alpha activity and matrix-degrading metalloproteinases in mammals using such compounds.