Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives.
Basic Information
ID: ALA1165919
Journal: Bioorg Med Chem
Title: Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives.
Authors: Navarrete-Vázquez G, Hidalgo-Figueroa S, Torres-Piedra M, Vergara-Galicia J, Rivera-Leyva JC, Estrada-Soto S, Estrada-Soto S, León-Rivera I, Aguilar-Guardarrama B, Rios-Gómez Y, Villalobos-Molina R, Ibarra-Barajas M.
Abstract: A series of 1H-benzo[d]imidazole analogues of Pimobendan, substituted at position 5 with either -CF(3) or -NO(2), were synthesized using a short synthetic route. All the nitro derivatives were potent, and exhibited a concentration- and partial endothelium-dependent vasorelaxant effects, with EC(50)s <5microM. 2-Methoxy-4-[5-nitro-1H-benzo[d]imidazol-2-yl]phenol (compound 13) was the most potent derivative of the series, showing an EC(50) value of 1.81microM 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-CF(3) analogue (compound 8), was 19 times less potent than 13. The antihypertensive activity of compound 13 was evaluated at doses of 25, 50 and 100mgkg(-1), using spontaneously hypertensive rats (SHR), showing a statistically significant dose-dependent effect.
CiteXplore: 20451399
DOI: 10.1016/j.bmc.2010.04.027
Patent ID: ┄