来源于 6-取代氨甲酰基和酰氨基苯并咪唑的非肽类血管紧张素 II AT₁ 受体拮抗剂。
Nonpeptidic angiotensin II AT₁ receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles.
机构信息
R&D Center for Pharmaceuticals, School of Chemical Engineering & The Environment, Beijing Institute of Technology, Beijing 100081, China.
出版信息
Eur J Med Chem. 2013 Nov;69:44-54. doi: 10.1016/j.ejmech.2013.08.014. Epub 2013 Aug 19.
Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT₁ receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT₁ receptor binding affinity and high AT₁ receptor selectivity over AT₂ receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT₁ IC₅₀ = 3 nM, AT₂ IC₅₀ > 10,000 nM, PA₂ = 8.51) and 11g (AT₁ IC₅₀ = 0.1 nM, AT₂ IC₅₀ = 149 nM, PA₂ = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT₁ receptor antagonists in spontaneous hypertensive rats.
设计并合成了 6-取代氨甲酰基和酰氨基苯并咪唑衍生物作为非肽类血管紧张素 II AT₁ 受体拮抗剂。在初步的药理学评价中，化合物 6f、6g、11e、11f、11g 和 12 表现出对 AT₁ 受体的纳摩尔结合亲和力和对 AT₂ 受体的高选择性。其中，两个最活性化合物 6f（AT₁ IC₅₀ = 3 nM，AT₂ IC₅₀ > 10,000 nM，PA₂ = 8.51）和 11g（AT₁ IC₅₀ = 0.1 nM，AT₂ IC₅₀ = 149 nM，PA₂ = 8.43）在分离的兔主动脉条功能测定中表现出良好的拮抗活性。此外，它们在自发性高血压大鼠中是具有口服活性的 AT₁ 受体拮抗剂。
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