HYDROXAMIC ACID DERIVATIVES, PROCESS FOR THEIR PREPARATION AND USE THEREOF

摘要

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 ASOnR<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 - C6alkyl) 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 OCH2COR<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 OCH2CH2OR<9> and R<4> is hydrogen; wherein R<9> is C1 - C6 alkyl, C1 - C6 alkylphenyl, phenyl, substituted phenyl, (C1 - C6 alkyl)acyl, or phenacyl; or R<3> is OCH2CN 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 rheumatoide arthritis, corneal ulceration, osteoporosis, periodontitis, gingivitis and tumour invasion.