Hydroxamic acid derivatives, process for their preparation...

C - Chemistry – Metallurgy – 07 – C

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C07C 259/06 (2006.01) A61K 31/165 (2006.01) A61K 31/33 (2006.01) C07C 237/22 (2006.01) C07C 323/47 (2006.01) C07C 323/60 (2006.01) C07D 207/36 (2006.01) C07D 213/70 (2006.01) C07D 237/18 (2006.01) C07D 239/38 (2006.01) C07D 307/64 (2006.01) C07D 333/24 (2006.01) C07D 333/34 (2006.01) C07F 7/10 (2006.01)

Patent

CA 2100661

2100661 9213831 PCTABS00014 Compounds of general formula (I): wherein R1 is hydrogen, C1-C6 alkyl, phenyl, substituted phenyl, phenyl(C1-C6 alkyl), or heterocyclyl; or R1 is ASOnR7 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; R7 is C1-C6 alkyl, phenyl, substituted phenyl, phenyl(C1-C6 alkyl), heterocyclyl, (C1-C6 alkyl)acyl thienyl or phenacyl; R2 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, phenyl (C1-C6 alkyl) or cycloalkyl(C1-C6 alkyl); R3 and R4 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 R3 is OCH2COR8 R4 is hydrogen; wherein R8 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 R3 is OCH2CH2OR9 and R4 is hydrogen; wherein R6 is C1-C6 alkyl, C1-C6 alkylphenyl, phenyl, substituted phenyl, (C1-C6 alkyl)acyl, or phenacyl; or R3 is OCH2CN and R4 is hydrogen; R5 is hydrogen or C1-C6 alkyl, or (C1-C6) alkylphenyl; R6 is hydrogen or methyl; or a salt thereof; specifically excluded are compounds wherein: R3 = R4 = hydrogen or R3 = R4 = hydroxy or R3 = hydrogen and R4 = oxybenzyl or R3 = hydrogen and R4 = 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.

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