非肽类AT2受体配体的微小结构改变导致功能活性的相互转换。
Interconversion of Functional Activity by Minor Structural Alterations in Nonpeptide AT2 Receptor Ligands.
作者信息
Wallinder Charlotta, Sköld Christian, Botros Milad, Guimond Marie-Odile, Hallberg Mathias, Gallo-Payet Nicole, Karlén Anders, Alterman Mathias
机构信息
Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University , SE-751 23 Uppsala, Sweden.
Beijer Laboratory, Department of Pharmaceutical Biosciences, BMC, Uppsala University SE-751 23 Uppsala, Sweden.
出版信息
ACS Med Chem Lett. 2014 Dec 8;6(2):178-82. doi: 10.1021/ml500427r. eCollection 2015 Feb 12.
Abstract
Migration of the methylene imidazole side chain in the first reported selective drug-like AT2 receptor agonist C21/M024 (1) delivered the AT2 receptor antagonist C38/M132 (2). We now report that the AT2 receptor antagonist compound 4, a biphenyl derivative that is structurally related to 2, is transformed to the agonist 6 by migration of the isobutyl group. The importance of the relative position of the methylene imidazole and the isobutyl substituent is highlighted herein.
摘要
在首个报道的选择性类药物AT2受体激动剂C21/M024（1）中，亚甲基咪唑侧链的迁移产生了AT2受体拮抗剂C38/M132（2）。我们现在报道，AT2受体拮抗剂化合物4（一种与2结构相关的联苯衍生物）通过异丁基的迁移转化为激动剂6。本文强调了亚甲基咪唑和异丁基取代基相对位置的重要性。
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