Preparation of 1-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective and bioavailable inhibitors of coagulation factor Xa

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

doi:10.1016/j.bmcl.2006.04.044

Preparation of 1-(4-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective and bioavailable inhibitors of coagulation factor Xa

Bioorg Med Chem Lett. 2006 Jul 15;16(14):3755-60. doi: 10.1016/j.bmcl.2006.04.044. Epub 2006 May 8.

Authors

John M Fevig¹, Joseph Cacciola, Joseph Buriak Jr, Karen A Rossi, 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. john.fevig@bms.com

PMID: 16682200
DOI: 10.1016/j.bmcl.2006.04.044

Abstract

Previously, potent factor Xa inhibitors were described based on a pyrazole core. Modifications of the pyrazole core have provided additional novel, highly potent factor Xa inhibitors. This manuscript will describe the synthesis and biological activity of factor Xa inhibitors containing the 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one and related bicyclic cores. Many of these compounds are potent, selective, and orally bioavailable inhibitors of coagulation factor Xa.

MeSH terms

Administration, Oral
Animals
Antithrombin III / chemical synthesis*
Antithrombin III / pharmacology
Biological Availability
Crystallography, X-Ray
Dogs
Factor Xa Inhibitors*
Fibrinolytic Agents / chemical synthesis*
Fibrinolytic Agents / pharmacology
Pyrazoles / chemical synthesis
Pyrazoles / pharmacology
Pyrimidinones / chemical synthesis*
Pyrimidinones / pharmacology
Thrombosis / drug therapy
Thrombosis / prevention & control

Substances

Factor Xa Inhibitors
Fibrinolytic Agents
Pyrazoles
Pyrimidinones
Antithrombin III