Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazole derivatives as nonpeptidic angiotensin II AT1 receptor antagonists.

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Citation

Wang JL, Zhang J, Zhou ZM, Li ZH, Xue WZ, Xu D, Hao LP, Han XF, Fei F, Liu T, Liang AH

Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazole derivatives as nonpeptidic angiotensin II AT1 receptor antagonists.

Eur J Med Chem. 2012 Mar;49:183-90. doi: 10.1016/j.ejmech.2012.01.009. Epub 2012 Jan 17.

PubMed ID
22309912 [ View in PubMed
]
Abstract

A series of 6-substituted aminocarbonyl benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed nanomolar AT(1) receptor binding affinity and good AT(1) receptor selectivity over AT(2) receptor for all compounds of the series, a potent antagonistic activity in isolated rabbit aortic strip functional assay for compounds 6b, 6d and 6i was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6i is an orally active AT(1) receptor antagonist with low toxicity.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
LosartanType-1 angiotensin II receptorIC 50 (nM)16.2N/AN/ADetails
TelmisartanType-1 angiotensin II receptorIC 50 (nM)1N/AN/ADetails