Broad spectrum matrix metalloproteinase inhibitors: An examination of succinamide hydroxamate inhibitors with P1 C(α) gem-disubstitution

Article abstract of DOI:10.1016/S0960-894X(98)00255-8

A series of P₁ C(α) gem-disubstituted succinamide hydroxamate matrix metalloproteinase inhibitors were prepared stereoselectively and evaluated 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 provided compounds that were broad spectrum inhibitors and nearly equipotent with parent inhibitor 1, a larger group such as bis-allyl as in 13 or gem-cyclopentyl as in 14 significantly reduced enzyme inhibition.