Preparation of 1-(3-aminobenzo[d]isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective, and efficacious inhibitors of coagulation factor Xa

Yun-Long Li; John M Fevig; Joseph Cacciola; Joseph Buriak Jr; Karen A Rossi; Janan Jona; Robert M Knabb; Joseph M Luettgen; Pancras C Wong; Stephen A Bai; Ruth R Wexler; Patrick Y S Lam

doi:10.1016/j.bmcl.2006.07.002

Preparation of 1-(3-aminobenzo[d]isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective, and efficacious inhibitors of coagulation factor Xa

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5176-82. doi: 10.1016/j.bmcl.2006.07.002. Epub 2006 Jul 25.

Authors

Yun-Long Li¹, John M Fevig, Joseph Cacciola, Joseph Buriak Jr, Karen A Rossi, Janan Jona, Robert M Knabb, Joseph M Luettgen, Pancras C Wong, Stephen A Bai, Ruth R Wexler, Patrick Y S Lam

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.

PMID: 16870435
DOI: 10.1016/j.bmcl.2006.07.002

Abstract

Previously, potent factor Xa inhibitors were described based on the 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one bicyclic core and a 4-methoxyphenyl P1 moiety. This manuscript describes 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one and related bicyclic cores with the 3-aminobenzisoxazole P1 moiety. Many of these compounds are potent, selective, and efficacious inhibitors of coagulation factor Xa.

MeSH terms

Anticoagulants / chemical synthesis*
Anticoagulants / pharmacology
Factor Xa Inhibitors*
Humans
Pyrimidinones / chemical synthesis*
Pyrimidinones / pharmacology*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / pharmacology
Structure-Activity Relationship
Substrate Specificity
Thromboembolism / drug therapy

Substances

Anticoagulants
Factor Xa Inhibitors
Pyrimidinones
Serine Proteinase Inhibitors