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

Philippe G. Nantermet; James C. Barrow; Stacey R. Lindsley; Marybeth Young; Shi Shan Mao; Steven Carroll; Carolyn Bailey; Michele Bosserman; Dennis Colussi; Daniel R. McMasters; Joseph P. Vacca; Harold G. Selnick

doi:10.1016/j.bmcl.2004.02.033

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

Philippe G. Nantermet, James C. Barrow, Stacey R. Lindsley, Marybeth Young, Shi Shan Mao, Steven Carroll, Carolyn Bailey, Michele Bosserman, Dennis Colussi, Daniel R. McMasters, Joseph P. Vacca, Harold G. Selnick

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2141-2145
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2004.02.033
State	Published - May 3 2004
Externally published	Yes

Keywords

Carboxypeptidase
Fibrinolysis
TAFI

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2004.02.033

Cite this

Nantermet, P. G., Barrow, J. C., Lindsley, S. R., Young, M., Mao, S. S., Carroll, S., Bailey, C., Bosserman, M., Colussi, D., McMasters, D. R., Vacca, J. P., & Selnick, H. G. (2004). Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P′₁ group. Bioorganic and Medicinal Chemistry Letters, 14(9), 2141-2145. https://doi.org/10.1016/j.bmcl.2004.02.033

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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.",

keywords = "Carboxypeptidase, Fibrinolysis, TAFI",

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T2 - SAR studies centered around the basic P′1 group

AU - Nantermet, Philippe G.

AU - Barrow, James C.

AU - Lindsley, Stacey R.

AU - Young, Marybeth

AU - Mao, Shi Shan

AU - Carroll, Steven

AU - Bailey, Carolyn

AU - Bosserman, Michele

AU - Colussi, Dennis

AU - McMasters, Daniel R.

AU - Vacca, Joseph P.

AU - Selnick, Harold G.

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KW - Carboxypeptidase

KW - Fibrinolysis

KW - TAFI

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