Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazole derivatives as nonpeptidic angiotensin II AT1 receptor antagonists

A series of 6-substituted aminocarbonyl benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT1 receptor antagonists. The preliminary pharmacological evaluation revealed nanomolar AT1 receptor binding affinity and good AT1 receptor selectivity over AT2 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 AT1 receptor antagonist with low toxicity.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 6-Substituted aminocarbonyl benzimidazole derivatives were designed and synthesised. ► Most compounds exhibited nanomolar AT1 receptor binding affinity. ► Compounds 6i were found to be the most potent compound. ► The toxicities of most compounds prepared appear to be as low as that of telmisartan.