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.
Subject(s)
Anticoagulants/chemical synthesis , Factor Xa Inhibitors , Pyrimidinones/chemical synthesis , Pyrimidinones/pharmacology , Serine Proteinase Inhibitors/chemical synthesis , Anticoagulants/pharmacology , Humans , Serine Proteinase Inhibitors/pharmacology , Structure-Activity Relationship , Substrate Specificity , Thromboembolism/drug therapyABSTRACT
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.
