Chlorothiophenecarboxamides as P1 surrogates of inhibitors of blood coagulation factor Xa

Bioorg Med Chem Lett. 2004 Dec 6;14(23):5817-22. doi: 10.1016/j.bmcl.2004.09.043.

Abstract

Neutral chlorothiophenecarboxamides bearing an amino acid and a substituted aniline were synthesized and investigated for their factor Xa inhibitory activity in vitro. From selected 2-methylphenyl morpholinones the solution properties were determined. The most soluble and active compounds were then investigated in different animal species to compare the pharmacokinetic parameters. This led to a potent, water soluble and orally bioavailable candidate for further development: EMD 495235.

MeSH terms

  • Animals
  • Dogs
  • Factor Xa / metabolism
  • Factor Xa Inhibitors*
  • Female
  • Macaca fascicularis
  • Male
  • Rats
  • Rats, Wistar
  • Serine Proteinase Inhibitors / chemistry*
  • Serine Proteinase Inhibitors / metabolism
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Thiophenes / chemistry*
  • Thiophenes / metabolism
  • Thiophenes / pharmacology

Substances

  • Factor Xa Inhibitors
  • Serine Proteinase Inhibitors
  • Thiophenes
  • Factor Xa