Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.
Bioorg Med Chem Lett. 2013 Feb 15;23(4):944-8. doi: 10.1016/j.bmcl.2012.12.050. Epub 2012 Dec 25.
(E)-2-(3-(3-((3-Bromophenyl)amino)-2-cyano-3-oxoprop-1-en-1-yl)-1H-indol-1-yl)acetic acid (1) was discovered in a HTS campaign for CRTh2 receptor antagonists. An SAR around this hit could be established and representatives with interesting activity profiles were obtained. Ring closing tactics to convert this hit series into a novel 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole based CRTh2 receptor antagonist series is presented.
(E)-2-(3-(3-((3-溴苯基)氨基)-2-氰基-3-氧代丙-1-烯-1-基)-1H-吲哚-1-基)乙酸（1）是在寻找 CRTh2 受体拮抗剂的高通量筛选中发现的。可以在这个命中物周围建立一个 SAR，并获得具有有趣活性特征的代表物。介绍了将这个命中物系列转化为新型 2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚基 CRTh2 受体拮抗剂系列的环合策略。
