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Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution.

作者信息

Curtin M L, Garland R B, Davidsen S K, Marcotte P A, Albert D H, Magoc T J, Hutchins C

机构信息

Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.

出版信息

Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8. doi: 10.1016/s0960-894x(98)00255-8.

DOI:10.1016/s0960-894x(98)00255-8
PMID:9873367
Abstract

A series of P1 C alpha 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.

摘要

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