Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P 1′ group

…, S Carroll, C Bailey, M Bosserman, D Colussi…

Index: Nantermet, Philippe G.; Barrow, James C.; Lindsley, Stacey R.; Young, Marybeth; Mao, Shi-Shan; Carroll, Steven; Bailey, Carolyn; Bosserman, Michele; Colussi, Dennis; McMasters, Daniel R.; Vacca, Joseph P.; Selnick, Harold G. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 9 p. 2141 - 2145

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Citation Number: 34

Abstract

Structural modifications of the aminopyridine P1′ group of imidazole acetic acid based TAFIa inhibitors led to the discovery of the aminocyclopentyl analog 28, a 1nM TAFIa inhibitor with CLT50 functional activity of 14nM but without selectivity against CPB. While not as active, aminobutyl derivative 27 provided an improved 6.7-fold selectivity for TAFIa versus CPB.