Design, synthesis and biological evaluation of AT1 receptor blockers derived from 6-substituted aminocarbonyl benzimidazoles

Abstract

A series of new 6-substituted aminocarbonyl benzimidazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole moiety and benzoic acid moiety were designed, synthesized and pharmacologically evaluated. Most of the synthesized compounds could bind to the AT₁ receptor and decrease blood pressure significantly. Notably, 2e and 1h could obviously decrease MBP in a dose dependent manner. The maximal response lowered 57.9 ± 2.3 mmHg (2e) and 57.6 ± 1.9 mmHg (1h) of MBP at 10 mg/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than Losartan (Fig. 1). These results indicate that 2e and 1h are effective and long-lasting anti-hypertension drug candidates and deserve further investigation for therapeutic application.

Keywords: AT(1) receptor blockers; Anti-hypertension drug; Hypertension.