HYDROXAMIC ACID DERIVATIVES AS METALLOPROTEINASE INHIBITORS

• Main Authors: CRIMMIN, MICHAEL JOHN, DICKENS, JONATHAN PHILIP, BECKETT, RAYMOND PAUL
• Format: Patent
• Language: English; French
• Published: 03.09.2002
• Edition: 6
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Compounds of formula (I) have matrix metalloproteinase inhibitory activity, wherein R2 represents a group R6-A- wher- ein A represents a divalent straight or branched, saturated or unsaturated hydrocarbon chain of up to 6 C atoms which may be interrupted by an O or S atom, and R6 represents hydrogen or an optionall y substituted phenyl, cycloalkyl or cycloalke- nyl group; R3 represents a group R7-(B)n- wherein n is 0 or 1, B represents a divalent straight or branched, saturated or un- saturated hydrocarbon chain of up to 6 C atoms which may be interrupted by a n O or S atom, and R7 is -CONHOH, car- boxyl, esterified or amidated carboxyl, cycloalkyl, cycloalkenyl, heterocyclyl, phenyl, naphtyl, or substituted phenyl or naphtyl in which the substituent(s) are selected from phenyl, hydroxy, C1-C6 alkoxy, benzyloxy, or R8-(C=O)-(C1-C6al- kyl)-O- wherein R8 is hydroxy, amino, or an amino acid residue linked via an amide bond; or (except when n=0) R7 is hy- drogen; R4 represents hydrogen or methyl; R5 represents hydrogen, C1-C6 alky l or a group D-(C1-C6 alkyl) wherein D re- presents hydroxy, (C1-C6)alkoxy, (C1-C6)alkylthio, acylamino, optionally substituted phenyl, or a heterocyclic group, NH2, or a mono- or di-(C1-NC6 alkyl) amine or a heterocyclic group; or R3 and R5 taken together represent a divalent, saturated or unsaturated hydrocarbon chain of from 8-14 C atoms, which may be interrupted by an O, S or N heteroatom, or a salt, solvate or hydrate thereof, provided that R3 is not the characteristic side chain of a natural alpha-amino acid, or the charac- teristic side chain of a natural alpha-amino acid in which any functional substituents are protected, any amino groups are acylated, and any carboxyl groups are esterified.