title: Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives.
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.
authors.affiliation: Universidad Autónoma del Estado de Morelos, Cuernavaca, Mor. 62209, Mexico. gabriel_navarrete@uaem.mx
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.forename: Sergio
authors.initials: S
authors.lastname: Hidalgo-Figueroa
authors.forename: Mariana
authors.initials: M
authors.lastname: Torres-Piedra
authors.forename: Jorge
authors.initials: J
authors.lastname: Vergara-Galicia
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Rivera-Leyva
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
authors.forename: Ismael
authors.initials: I
authors.lastname: León-Rivera
authors.forename: Berenice
authors.initials: B
authors.lastname: Aguilar-Guardarrama
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Rios-Gómez
authors.forename: Rafael
authors.initials: R
authors.lastname: Villalobos-Molina
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ibarra-Barajas
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011724:Pyridazines; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D011724:Pyridazines; D014665:Vasodilator Agents; C041648:pimobendan