| abstract |
This invention relates to matrix metalloproteinase (MMP) inhibiting compounds ofnthe formula:n nwhere R 1 is C 1 -C 12 alkyl, straight or branched and optionally substituted by halogen,nhydroxy, C 1 -C 6 alkoxy, amino, carboxyl, C 1 -C 6 alkoxycarbonyl, carboxamido, nitrile,nmono- or di-(C 1 -C 6 )alkylamino, thio, C 1 -C 6 alkylthio, aryl, -Oaryl or -OCH 2 aryl wherenaryl is optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 alkoxy, carboxy, halogen, cyano,nnitro, carboxamido, or hydroxy; and C 1 -C 6 alkanesulfonyloxy. R 2 is α-OH or β-OH andnR 6 is H or R 2 and R 6 together are carbonyl; the chemical intermediates; and processes fornthe preparation of these compounds and the intermediates thereto. n Matrix metalloproteinases (MMP) are a family of zinc-containing calcium dependentnproteinases, including stromelysins, collagenases, and gelatinases. These MMP enzymesnare capable of degrading the proteinaceous components of connective tissue and appear tonbe involved in tissue remodeling, i.e., wound healing and connective tissue turnover.nUnexpectedly, the mercaptoalcohols with the S-configuration at the hydroxyl-bearingncarbon have been found to be at least 4 times more potent than the analogous (R)-alcoholsnboth in vitro and in vivo in inhibiting the MMP enzyme.. |