Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Japan.
Bioorg Med Chem. 2011 Jan 15;19(2):883-93. doi: 10.1016/j.bmc.2010.12.002. Epub 2010 Dec 6.
The design, synthesis and structure-activity relationships of a novel class of N-phenylpyridone MCH1R antagonists are described. The core part of the N-phenylpyridone structure was newly designed and the side chain moieties that were attached to the core part were extensively explored. As a result of optimization of the N-phenylpyridone leads, we successfully developed the orally available, and brain-penetrable MCH1R selective antagonist 7c, exhibiting excellent anti-obese effect in diet-induced obese (DIO) mice.
本文描述了一类新型 N-苯基吡啶酮 MCH1R 拮抗剂的设计、合成及构效关系。新设计了 N-苯基吡啶酮结构的核心部分，并广泛探索了连接到核心部分的侧链部分。通过对 N-苯基吡啶酮先导化合物的优化，我们成功开发出了可口服、可穿透血脑屏障的 MCH1R 选择性拮抗剂 7c，在饮食诱导肥胖（DIO）小鼠中表现出优异的抗肥胖效果。
