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

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5263-7. doi: 10.1016/j.bmcl.2004.08.034.

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.

Publication types

  • Comparative Study

MeSH terms

  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Binding Sites
  • Crystallography, X-Ray
  • Factor IXa / antagonists & inhibitors*
  • Factor IXa / chemistry*
  • Factor Xa / chemistry*
  • Factor Xa Inhibitors*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • Factor Xa Inhibitors
  • Pyrazoles
  • Factor IXa
  • Factor Xa