Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives.
Bioorg Med Chem
; 18(11): 3985-91, 2010 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-20451399
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.
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1
Base de dados:
MEDLINE
Assunto principal:
Vasodilatadores
/
Imidazóis
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Anti-Hipertensivos
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article