Selective angiotensin II AT2 receptor agonists devoid of the imidazole ring system
- 作者：A.M.S. Murugaiah ; Chalotta Wallinder ; A.K. Mahalingam ; Xiongyu Wu ; Yiqian Wan ; Bianca Plouffe ; Milad Botros ; Anders Karlé ; n ; Mathias Hallberg ; Nicole Gallo-Payet ; Mathias Alterman
- 关键词：Angiotensin ; AT2 ; Agonist
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 November 2007
- 卷：15
- 期：22
- 页码：7166-7183
- 文件大小：363 K
摘要
A versatile parallel synthetic method to obtain three series of non-cyclic analogues of the first drug-like selective angiotensin II AT2 receptor agonist (1) has been developed. In analogy with the transformation of losartan to valsartan it was demonstrated that a non-cyclic moiety could be employed as an imidazole replacement to obtain AT2 selective compounds. In all the three series, AT2 receptor ligands with affinities in the lower nanomolar range were found. None of the analogues exhibited any affinity for the AT1 receptor. Four compounds, 17, 22, 39 and 51, were examined in a neurite outgrowth cell assay. All four compounds were found to exert a high agonistic effect as deduced from their capacity to induce neurite elongation in neuronal cells, as does angiotensin II.