Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives

Article abstract of DOI:10.1016/j.bmc.2010.04.027

A series of 1H-benzo[d]imidazole analogues of Pimobendan, substituted at position 5 with either -CF₃ or -NO₂, were synthesized using a short synthetic route. All the nitro derivatives were potent, and exhibited a concentration- and partial endothelium-dependent vasorelaxant effects, with EC₅₀s <5 μM. 2-Methoxy-4-[5-nitro-1H-benzo[d]imidazol-2-yl]phenol (compound 13) was the most potent derivative of the series, showing an EC₅₀ value of 1.81 μM and E_max of 91.7% for ex vivo relaxant response in intact aortic rings, resulting in a 2.5-fold higher activity compared to Pimobendan. The closely related 5-CF₃ analogue (compound 8), was 19 times less potent than 13. The antihypertensive activity of compound 13 was evaluated at doses of 25, 50 and 100 mg kg^-1, using spontaneously hypertensive rats (SHR), showing a statistically significant dose-dependent effect.