Design, synthesis, and biological activity of novel purine and bicyclic pyrimidine factor Xa inhibitors.
The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin.
Buckman
B O
BO
Berlex Biosciences, Richmond, CA 94804, USA.
Mohan
R
R
Koovakkat
S
S
Liang
A
A
Trinh
L
L
Morrissey
M M
MM
D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002417:Cattle; D015195:Drug Design; D015951:Factor Xa / Q000737:chemistry; D065427:Factor Xa Inhibitors; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011487:Protein Conformation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D007202:Indicators and Reagents; D011743:Pyrimidines; D014361:Trypsin Inhibitors; D013917:Thrombin; D015951:Factor Xa