Design, synthesis, and structure-activity relationship of a new class of amidinophenylurea-based factor VIIa inhibitors

Bioorg Med Chem Lett. 2003 Apr 17;13(8):1463-7. doi: 10.1016/s0960-894x(03)00168-9.

Abstract

Selective inhibition of coagulation factor VIIa has recently gained attraction as interesting approach towards antithrombotic treatment. Using parallel synthesis supported by structure-based design and X-ray crystallography, we were able to identify a novel series of amidinophenylurea derivatives with remarkable affinity for factor VIIa. The most potent compound displays a K(i) value of 23 nM for factor VIIa.

MeSH terms

  • Crystallography, X-Ray
  • Drug Design
  • Factor VIIa / antagonists & inhibitors*
  • Humans
  • Models, Molecular
  • Phenylurea Compounds / chemical synthesis*
  • Phenylurea Compounds / chemistry
  • Phenylurea Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Phenylurea Compounds
  • Factor VIIa