Phenyltriazolinones as potent factor Xa inhibitors

We have discovered that phenyltriazolinone is a novel and potent P 1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P 1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S 1 binding pocket which is larger in size to accommodate the phenyltriazolinone P 1 substrate. We have discovered that phenyltriazolinone is a novel and potent P 1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P 1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S 1 binding pocket which is larger in size to accommodate the phenyltriazolinone P 1 substrate.