EP0780386A1 — Matrix metalloprotease inhibitors

USPTO Abstract

Compounds of the formula: wherein: n is 0, 1 or 2; Y is hydroxy or XONH-, where X is hydrogen or lower alkyl; R 1 is hydrogen or lower alkyl; R 2 is hydrogen, lower alkyl, heteroalkyl, aryl, aralkyl, arylheteroalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heteroarylheteroalkyl, heterocyclo, heterocylo-lower alkyl, heterocyclo-lower heteroalkyl or -NR 6 R 7 , wherein: R 6 is hydrogen, lower alkyl, cycloalkyl or cycloalkylalkyl, aryl, heteroaryl and heteroaralkyl; R 7 is hydrogen, lower alkyl, cycloalkyl or cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, -C(O)R 8 , -C(O)NR 8 R 9 , -SO 2 NR 8 R 9 , -SO 2 R 10 , aryloxycarbonyl, or alkoxycarbonyl; or R 6 and R 7 together with the nitrogen atom to which they are attached represent a heterocyclo group; wherein R 8 and R 9 are independently hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl or heteroalkyl; and R 10 is lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heteroalkyl or heterocyclo; or R 1 and R 2 together with the carbon atom to which they are attached represent a cycloalkyl or heterocyclo group; R 3 is hydrogen, lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heteroalkyl or lower alkoxy; R 4 is hydrogen, lower alkyl, cycloalkyl or cycloalkylalkyl; or R 2 and R 3 together with the carbons to which they are attached represent a cycloalkyl or heterocyclo group; or R 3 and R 4 together with the carbon to which they are attached represent a cycloalkyl or heterocyclo group; and R 5 is lower alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; or pharmaceutically acceptable salts or esters thereof exhibit useful pharmacological properties, in particular for use as matrix metalloprotease inhibitors, particularly for interstitial collagenases.