Solid-phase synthesis of naphthylamidines as factor VIIa/tissue factor inhibitors

Bioorg Med Chem Lett. 2005 May 2;15(9):2249-52. doi: 10.1016/j.bmcl.2005.03.019.

Abstract

Reductive amination followed by acylation of polymer-linked formyl aryl amidines generate combinatorial libraries of aryl amidines 8-13. Potent small molecule naphthylamidine inhibitors 12 (Ki<100 nM) of FVIIa/TF have been discovered and their activity against other serine proteases in the coagulation cascade is reported.

MeSH terms

  • Amidines / chemical synthesis*
  • Amidines / chemistry
  • Amidines / pharmacology
  • Binding Sites
  • Factor VIIa / antagonists & inhibitors*
  • Humans
  • Kinetics
  • Models, Molecular
  • Molecular Conformation
  • Naphthols / chemical synthesis
  • Naphthols / chemistry
  • Naphthols / pharmacology
  • Structure-Activity Relationship
  • Thromboplastin / antagonists & inhibitors*

Substances

  • Amidines
  • Naphthols
  • Thromboplastin
  • Factor VIIa