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.
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.
Li
Yun-Long
YL
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
Fevig
John M
JM
Cacciola
Joseph
J
Buriak
Joseph
J
Rossi
Karen A
KA
Jona
Janan
J
Knabb
Robert M
RM
Luettgen
Joseph M
JM
Wong
Pancras C
PC
Bai
Stephen A
SA
Wexler
Ruth R
RR
Lam
Patrick Y S
PY
D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology; D065427:Factor Xa Inhibitors; D006801:Humans; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013923:Thromboembolism / Q000188:drug therapy
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011744:Pyrimidinones; D015842:Serine Proteinase Inhibitors