Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P(1)(') group.
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.
Nantermet
Philippe G
PG
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. philippe_nantermet@merck.com
Barrow
James C
JC
Lindsley
Stacey R
SR
Young
MaryBeth
M
Mao
Shi-Shan
SS
Carroll
Steven
S
Bailey
Carolyn
C
Bosserman
Michele
M
Colussi
Dennis
D
McMasters
Daniel R
DR
Vacca
Joseph P
JP
Selnick
Harold G
HG
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
D004791:Enzyme Inhibitors; D007093:Imidazoles; C029899:imidazole; D025901:Carboxypeptidase B2