Discovery of inhibitors of plasminogen activator inhibitor-1: structure-activity study of 5-nitro-2-phenoxybenzoic acid derivatives

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5701-6. doi: 10.1016/j.bmcl.2011.08.031. Epub 2011 Aug 11.

Abstract

Two novel series of 5-nitro-2-phenoxybenzoic acid derivatives are designed as potent PAI-1 inhibitors using hybridization and conformational restriction strategy in the tiplaxtinin and piperazine chemo types. The lead compounds 5a, 6c, and 6e exhibited potent PAI-1 inhibitory activity and favorable oral bioavailability in the rodents.

MeSH terms

  • Administration, Oral
  • Animals
  • Benzoates / chemistry*
  • Benzoates / pharmacokinetics
  • Benzoates / pharmacology*
  • Biological Availability
  • Disease Models, Animal
  • Drug Design*
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Indoleacetic Acids / chemistry
  • Indoleacetic Acids / pharmacology
  • Male
  • Molecular Structure
  • Phenyl Ethers / chemistry*
  • Phenyl Ethers / pharmacokinetics
  • Phenyl Ethers / pharmacology
  • Piperazine
  • Piperazines / chemistry
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Thrombosis / chemically induced
  • Thrombosis / drug therapy

Substances

  • Benzoates
  • Indoleacetic Acids
  • Phenyl Ethers
  • Piperazines
  • Plasminogen Activator Inhibitor 1
  • tiplaxtinin
  • Piperazine