R&D Center for Pharmaceuticals, School of Chemical Engineering & the Environment, Beijing Institute of Technology, Beijing, China.
Eur J Med Chem. 2012 Mar;49:183-90. doi: 10.1016/j.ejmech.2012.01.009. Epub 2012 Jan 17.
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.
设计并合成了一系列 6-取代氨基羰基苯并咪唑衍生物作为非肽类血管紧张素 II AT(1)受体拮抗剂。初步的药理学评价表明，该系列所有化合物均具有纳摩尔级的 AT(1)受体结合亲和力和良好的 AT(1)受体选择性，对 AT(2)受体的选择性优于 AT(2)受体，化合物 6b、6d 和 6i 在离体兔主动脉条功能测定中也表现出很强的拮抗活性。此外，在自发性高血压大鼠中的评价和初步毒性评价表明，化合物 6i 是一种具有低毒性的口服有效的 AT(1)受体拮抗剂。
