HYDROXAMIC AND CARBOXYLIC ACIDS AS METALLOPROTEASE INHIBITORS

摘要

The present invention provides hydroxamic acids and carbocyclic acids and derivatives thereof and to pharmaceutical compositions and methods of use of these compounds for the inhibition of matrix metalloproteinases, such as stromelysin, and inhibit the production of tumor necrosis factor alpha, and for the treatment of arthritis and other inflammatory diseases. These compounds are represented by formula (I), wherein: A is -C(R<1>) (R<1a>)CONHOH or -CH(R<11>)C(R<9>)(R<9a>)CO2H; Q is CONHR<13>; R<2> is selected from: C1-C8 alkyl substituted with O-2R<17b>; -O-(C1-C8 alkyl)-R<20>; -S-(C1-C8 alkyl)-R<20>; -CH2O-(C1-C8 alkyl)-R<20>; -CH2S-(C1-C8 alkyl)-R<20>; R<3> is selected from hydrogen, or C1-C6 alkyl substituted with 0-3 R<4>; R<14> is selected from hydrogen, methyl or ethyl.