title: Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution.
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.
authors.affiliation: Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Curtin
authors.forename: R B
authors.initials: RB
authors.lastname: Garland
authors.forename: S K
authors.initials: SK
authors.lastname: Davidsen
authors.forename: P A
authors.initials: PA
authors.lastname: Marcotte
authors.forename: D H
authors.initials: DH
authors.lastname: Albert
authors.forename: T J
authors.initials: TJ
authors.lastname: Magoc
authors.forename: C
authors.initials: C
authors.lastname: Hutchins
mesh_terms: D000818:Animals; D006877:Hydroxamic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats
chemical_list: D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D008666:Metalloendopeptidases