Angiotensin II--AT1 receptor antagonists: design, synthesis and evaluation of substituted carboxamido benzimidazole derivatives

Eur J Med Chem. 2008 Sep;43(9):1808-12. doi: 10.1016/j.ejmech.2007.11.008. Epub 2007 Nov 22.

Abstract

A series of 5-(alkyl and aryl)carboxamido benzimidazole derivatives had been designed, synthesized and evaluated for in vitro angiotensin II--AT1 receptor antagonism and in vivo antihypertensive activities. The pharmacological activities were inversely related to the size of alkyl and aryl substituents. It can be suggested that compounds with lower alkyl groups at 5-position of benzimidazole nucleus demonstrated potent antihypertensive activity.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / chemical synthesis*
  • Angiotensin II Type 1 Receptor Blockers / chemistry
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / therapeutic use
  • Drug Design*
  • Hypertension / drug therapy
  • Rats
  • Receptor, Angiotensin, Type 1*
  • Reference Standards

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Benzimidazoles
  • Receptor, Angiotensin, Type 1