Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives.
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.
Navarrete-Vázquez
Gabriel
G
Universidad Autónoma del Estado de Morelos, Cuernavaca, Mor. 62209, Mexico. gabriel_navarrete@uaem.mx
Hidalgo-Figueroa
Sergio
S
Torres-Piedra
Mariana
M
Vergara-Galicia
Jorge
J
Rivera-Leyva
Julio Cesar
JC
Estrada-Soto
Samuel
S
León-Rivera
Ismael
I
Aguilar-Guardarrama
Berenice
B
Rios-Gómez
Yolanda
Y
Villalobos-Molina
Rafael
R
Ibarra-Barajas
Maximiliano
M
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
D000959:Antihypertensive Agents; D007093:Imidazoles; D011724:Pyridazines; D014665:Vasodilator Agents; C041648:pimobendan