1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 2: A survey of P4 motifs

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1221-7. doi: 10.1016/j.bmcl.2003.12.053.

Abstract

A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (K(i)< or =2 nM) with improved in vitro anticoagulant activity (2xTG< or =1 microM) and respectable pharmacokinetic properties have been discovered.

MeSH terms

  • Amides / chemistry*
  • Amides / metabolism
  • Amides / pharmacology
  • Animals
  • Antithrombin III / chemistry*
  • Antithrombin III / metabolism
  • Antithrombin III / pharmacology
  • Factor Xa Inhibitors*
  • Humans
  • Protein Binding
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Amides
  • Factor Xa Inhibitors
  • Pyrazoles
  • pyrazole
  • Antithrombin III