Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6538-41. doi: 10.1016/j.bmcl.2010.09.038. Epub 2010 Sep 16.

Abstract

A new class of 2-substituted benzoxazole carboxamides are presented as potent functional 5-HT(3) receptor antagonists. The chemical series possesses nanomolar in vitro activity against human 5-HT(3)A receptors. A chemistry optimization program was conducted and identified 2-aminobenzoxazoles as orally active 5-HT(3) receptor antagonists with good metabolic stability. These novel analogues possess drug-like characteristics and have potential utility for the treatment of diseases attributable to improper 5-HT(3) receptor function, especially diarrhea predominant irritable bowel syndrome (IBS-D).

MeSH terms

  • Benzoxazoles / chemistry*
  • Benzoxazoles / pharmacology*
  • Drug Discovery*
  • Receptors, Serotonin, 5-HT3 / drug effects*
  • Serotonin Antagonists / chemistry*
  • Serotonin Antagonists / pharmacology*

Substances

  • Benzoxazoles
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists