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ID: ALA1137915

Journal: Bioorg Med Chem Lett

Title: SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa.

Authors: Smallheer JM, Alexander RS, Wang J, Wang S, Nakajima S, Rossi KA, Smallwood A, Barbera F, Burdick D, Luettgen JM, Knabb RM, Wexler RR, Jadhav PK.

Abstract: Modifications to the P4 moiety and pyrazole C3 substituent of factor Xa inhibitor SN-429 provided several new compounds, which are 5-10nM inhibitors of factor IXa. An X-ray crystal structure of one example complexed to factor IXa shows that these compounds adopt a similar binding mode to that previously observed with pyrazole inhibitors in the factor Xa active site both with regard to how the inhibitor binds and the position of Tyr99.

CiteXplore: 15454208

DOI: 10.1016/j.bmcl.2004.08.034