Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT(1) receptor antagonists.

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

Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT(1) receptor antagonists.

Bioorg Med Chem. 2012 Jul 15;20(14):4208-16. doi: 10.1016/j.bmc.2012.05.056. Epub 2012 Jun 5.

PubMed ID
22727371 [ View in PubMed
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Abstract

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g 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
LosartanType-1 angiotensin II receptorIC 50 (nM)0.33N/AN/ADetails
TelmisartanType-1 angiotensin II receptorIC 50 (nM)1N/AN/ADetails
TelmisartanType-1 angiotensin II receptorIC 50 (nM)150N/AN/ADetails