Cinnamylindoline derivatives: synthesis and factor Xa (FXa) inhibitory activities

Chem Pharm Bull (Tokyo). 2007 Oct;55(10):1494-504. doi: 10.1248/cpb.55.1494.

Abstract

A series of cinnamylindoline derivatives were synthesized, and their factor Xa (FXa) inhibitory activities and selectivity over trypsin were evaluated. Among them, some novel derivatives showed potent FXa inhibitory activities and good selectivity over trypsin. Especially, (E)-2-{5-[1-(acetimidoyl)piperidin-4-yloxy]-2-[2-(5-amidino-2-hydroxyphenyl)ethen-1-yl]indolin-1-ylsulfonyl}acetic acid (22f) having 2-hydroxycinnamyl moiety exhibited the most potent FXa inhibitory activity in vitro. Furthermore, 22f also exhibited potent anticoagulant activities in vitro.

MeSH terms

  • Anticoagulants / chemical synthesis
  • Anticoagulants / pharmacology*
  • Cinnamates / chemical synthesis
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Factor Xa Inhibitors*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Structure-Activity Relationship
  • Trypsin / metabolism

Substances

  • Anticoagulants
  • Cinnamates
  • Factor Xa Inhibitors
  • Indoles
  • Trypsin