Design, synthesis, and SAR of substituted acrylamides as factor Xa inhibitors

Bioorg Med Chem Lett. 2002 Jun 3;12(11):1511-5. doi: 10.1016/s0960-894x(02)00199-3.

Abstract

Substituted acrylamides were used as templates that bridge P1 and P4 binding elements, resulting in a series of potent (sub-nanomolar) and selective factor Xa inhibitors. In this template, cis-geometry of P1 and P4 ligands is highly preferred. SAR on the substituting groups, as well as on modification of P1 and P4 moieties is described. Compounds in this series show good in vivo efficacy in animal models.

Publication types

  • Comparative Study

MeSH terms

  • Acrylamides / chemical synthesis*
  • Acrylamides / chemistry
  • Acrylamides / pharmacology*
  • Animals
  • Antithrombin III / chemical synthesis*
  • Antithrombin III / chemistry
  • Antithrombin III / pharmacology*
  • Binding Sites
  • Biological Availability
  • Disease Models, Animal
  • Drug Design
  • Factor Xa Inhibitors*
  • Ligands
  • Models, Molecular
  • Rabbits
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Templates, Genetic
  • Thrombosis / drug therapy

Substances

  • Acrylamides
  • Factor Xa Inhibitors
  • Ligands
  • Antithrombin III