Design, synthesis, and structure-activity relationships of substituted piperazinone-based transition state factor Xa inhibitors.
The structure-activity relationship of a novel series of substituted piperazinone-based factor Xa inhibitors is described. The most potent compound 34 displays IC(50) of 0.9 nM.
Su
Ting
T
Department of Medicinal Chemistry, Millennium Pharmaceuticals Inc., 256 East Grand Avenue, South San Francisco, CA 94080, USA.
Yang
Hua
H
Volkots
Deborah
D
Woolfrey
John
J
Dam
Suiko
S
Wong
Paul
P
Sinha
Uma
U
Scarborough
Robert M
RM
Zhu
Bing-Yan
BY
D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry; D001665:Binding Sites; D015195:Drug Design; D065427:Factor Xa Inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D010879:Piperazines; D015842:Serine Proteinase Inhibitors; D013917:Thrombin