| abstract |
Compounds of general formula (I): wherein R?1 is hydrogen, C1?-C6? alkyl, phenyl, substituted phenyl, phenyl(C1?-C6? alkyl), or heterocyclyl; or R?1 is ASOn?R?7 wherein A represents a C1?-C6? hydrocarbon chain, optionally substituted with one or more C1?-C6? alkyl, phenyl or substituted phenyl groups n = 0, 1, 2; R?7 is C1?-C6? alkyl, phenyl, substituted phenyl, phenyl(C1?-C6? alkyl), heterocyclyl, (C1?-C6? alkyl)acyl thienyl or phenacyl; R?2 is hydrogen, C1?-C6? alkyl, C2?-C6? alkenyl, phenyl (C1?-C6? alkyl) or cycloalkyl(C1?-C6? alkyl); R?3 and R?4 are selected from hydrogen, halogen, cyano amino, amino(C1?-C6?)alkyl, amino di (C1?-C6?)alkyl, amino(C1?-C6?)alkylacyl, aminophenacyl, amino (substituted phenacyl, amino acid or derivative thereof, hydroxy, oxy(C1?-C6?)alkyl, oxyacyl, formyl, carboxylic acid, carboxamide, carboxy (C1?-C6?) alkylamide, carboxyphenylamide, carboxy(C1?-C6?) alkyl, hydroxy(C1?-C6?)alkyl, (C1?-C6?)alkyloxy(C1?-C6?) alkyl or acyloxy(C1?-C6?)alkyl, (C1?-C6?)alkylcarboxylic acid, (C1?-C6?) alkylcarboxy (C1?-C6?) alkyl, amino (C1-6?)alkylacyl carboxylic acid or amino (C1-6?)alkylacyl (C1-6?) alkylcarboxylate; or R?3 is OCH2?COR?8 R?4 is hydrogen; wherein R?8 is hydroxyl, C1?-C6? oxyalkyl, C1?-C6? oxyalkylphenyl, amino, C1?-C6? aminoalkyl, C1?-C6? aminodialkyl, C1?-C6? aminoalkylphenyl, an amino acid or derivative thereof; or R?3 is OCH2?CH2?OR?9 and R?4 is hydrogen; wherein R?6 is C1?-C6? alkyl, C1?-C6? alkylphenyl, phenyl, substituted phenyl, (C1?-C6? alkyl)acyl, or phenacyl; or R?3 is OCH2?CN and R?4 is hydrogen; R?5 is hydrogen or C1?-C6? alkyl, or (C1?-C6?) alkylphenyl; R?6 is hydrogen or methyl; or a salt thereof; specifically excluded are compounds wherein: R?3 = R?4 = hydrogen or R?3 = R?4 = hydroxy or R?3 = hydrogen and R?4 = oxybenzyl or R?3 = hydrogen and R?4 = oxy(C1?-C6? alkyl); or a salt thereof; have collagenase inhibition activity and are useful in the management of disease involving collagen degradation. Its uses include rheumatoid arthritis, corneal ulceration, osteoporosis, periodontitis, gingivitis and tumour invasion. |