Department of Medicinal Chemistry, Merck Research Laboratory, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett. 2013 Jan 15;23(2):466-71. doi: 10.1016/j.bmcl.2012.11.055. Epub 2012 Nov 29.
In an attempt to further improve overall profiles of the oxadiazine series of GSMs, in particular the hERG activity, conformational modifications of the core structure resulted in the identification of fused oxadiazepines such as 7i which had an improved hERG inhibition profile and was a highly efficacious GSM in vitro and in vivo in rats. These SAR explorations offer opportunities to identify potential drugs to treat Alzheimer's disease.
为了进一步提高恶二嗪系列 GSMs 的整体特性，特别是 hERG 活性，对核心结构进行构象修饰，得到了稠合恶二嗪类化合物，如 7i，其 hERG 抑制谱得到改善，并且在大鼠体内外均具有高效的 GSM 活性。这些 SAR 研究为寻找治疗阿尔茨海默病的潜在药物提供了机会。
