Synthesis and evaluation of acylguanidine FXa inhibitors

A series of acylguanidine derivatives were prepared and investigated as inhibitors of Factor Xa (FXa). These compounds were made by guanidine acylation with carboxylic acids using carbonyl diimidazole (CDI) as the coupling reagent. Conditions for the rapid synthesis and purification of these compoun...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2008-08, Vol.18 (16), p.4696-4699
Main Authors: O’Connor, Stephen P., Atwal, Karnail, Li, Chi, Liu, Eddie C.-K., Seiler, Steven M., Shi, Mengxiao, Shi, Yan, Stein, Philip D., Wang, Ying
Format: Article
Language:English
Subjects:
Anticoagulants - chemical synthesis
Anticoagulants - pharmacology
Antithrombin III - chemical synthesis
Antithrombin III - pharmacology
Biological and medical sciences
Blood Coagulation
Blood. Blood coagulation. Reticuloendothelial system
Carboxylic Acids - chemistry
Chemistry, Pharmaceutical - methods
Coagulation
Drug Design
Factor Xa
Factor Xa - chemistry
Guanidines - chemical synthesis
Guanidines - pharmacology
Guanine - chemistry
Humans
Imidazoles - chemistry
Inhibitory Concentration 50
Medical sciences
Models, Chemical
Molecular Structure
Pharmacology. Drug treatments
Serine protease
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Summary:A series of acylguanidine derivatives were prepared and investigated as inhibitors of Factor Xa (FXa). These compounds were made by guanidine acylation with carboxylic acids using carbonyl diimidazole (CDI) as the coupling reagent. Conditions for the rapid synthesis and purification of these compounds are described along with their ability to inhibit FXa. The best FXa inhibitor is 1 with a FXa IC 50 of 6 nM.
ISSN:0960-894X
0968-0896
1464-3405
1464-3391
DOI:10.1016/j.bmcl.2008.07.004