Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazole derivatives as nonpeptidic angiotensin II AT ₁ receptor antagonists

A series of 6-substituted aminocarbonyl benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT ₁ receptor antagonists. The preliminary pharmacological evaluation revealed nanomolar AT ₁ receptor binding affinity and good AT ₁ receptor selectivity over AT ₂ receptor for all compounds of the series, a potent antagonistic activity in isolated rabbit aortic strip functional assay for compounds 6b, 6d and 6i was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6i is an orally active AT ₁ receptor antagonist with low toxicity.