BROAD-SPECTRUM MATRIX METALLOPROTEINASE INHIBITORS - AN EXAMINATION OF SUCCINAMIDE HYDROXAMATE INHIBITORS WITH P1C-ALPHA GEM-DISUBSTITUTION

A series of P-1 C-alpha gem-disubstituted succinamide hydroxamate matr ix metalloproteinase inhibitors were prepared stereoselectively and ev aluated in vitro for their ability to inhibit MMP-1, MMP-2, and MMP-3. It was found that while methyl/allyl substitution as in 2 and 18 prov ided compounds that were broad spectrum inhibitors and nearly equipote nt with parent inhibitor 1, a larger group such as bis-allyl as in 13 or gem-cyclopentyl as in 14 significantly reduced enzyme inhibition. ( C) 1998 Elsevier Science Ltd. All rights reserved.