title: Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P(1)(') group.
abstract: Structural modifications of the aminopyridine P(1)(') group of imidazole acetic acid based TAFIa inhibitors led to the discovery of the aminocyclopentyl analog 28, a 1 nM TAFIa inhibitor with CLT(50) functional activity of 14 nM but without selectivity against CPB. While not as active, aminobutyl derivative 27 provided an improved 6.7-fold selectivity for TAFIa versus CPB.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. philippe_nantermet@merck.com
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Nantermet
authors.forename: James C
authors.initials: JC
authors.lastname: Barrow
authors.forename: Stacey R
authors.initials: SR
authors.lastname: Lindsley
authors.forename: MaryBeth
authors.initials: M
authors.lastname: Young
authors.forename: Shi-Shan
authors.initials: SS
authors.lastname: Mao
authors.forename: Steven
authors.initials: S
authors.lastname: Carroll
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bailey
authors.forename: Michele
authors.initials: M
authors.lastname: Bosserman
authors.forename: Dennis
authors.initials: D
authors.lastname: Colussi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: McMasters
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacca
authors.forename: Harold G
authors.initials: HG
authors.lastname: Selnick
mesh_terms: D025901:Carboxypeptidase B2 / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; C029899:imidazole; D025901:Carboxypeptidase B2