Merck Research Laboratories Boston, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
Bioorg Med Chem Lett. 2012 May 1;22(9):3140-6. doi: 10.1016/j.bmcl.2012.03.054. Epub 2012 Mar 21.
Synthesis and SAR studies of novel aryl triazoles as gamma secretase modulators (GSMs) are presented in this communication. Starting from our aryl triazole leads, optimization studies were continued and the series progressed towards novel amides and lactams. Triazole 57 was identified as the most potent analog in this series, displaying single-digit nanomolar Aβ42 IC(50) in cell-based assays and reduced affinity for the hERG channel.
本通讯介绍了新型芳基三唑类γ分泌酶调节剂（GSMs）的合成和 SAR 研究。从我们的芳基三唑先导化合物开始，继续进行优化研究，该系列化合物进一步发展为新型酰胺和内酰胺。三唑 57 被确定为该系列中最有效的类似物，在基于细胞的测定中显示出单个位数纳摩尔的 Aβ42 IC（50），并且对 hERG 通道的亲和力降低。
