Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT1 receptor antagonists

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT1 receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT1 receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT1 receptor antagonist with low toxicity.

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised. The in vitro and in vivo evaluation results showed that compound 6g is an orally active AT1 receptor antagonist with low toxicity.Figure optionsDownload as PowerPoint slide