Inhibitors of MMP-1: An examination of P-1'C-alpha gem-disubstitution in the succinamide hydroxamate series

The effect of P-1' C-alpha gem-disubstitution in a series of succinamide hydroxamate inhibitors of MMP-1 has been investigated. While in all cases P-1' gem-disubstitution led to loss of potency relative to the corresponding P-1' isobutyl and phenyl compounds 1 and 3, respectively, the loss of activity was less pronounced in certain instances, e.g., the P-1' gem-cyclohexyl analogue 12 (IC50 = 0.15 mu M). Copyright (C) 1996 Elsevier Science Ltd