基于螺环吲哚烷的酰胺类化合物作为有效的、选择性的 MC4R 激动剂，用于治疗肥胖症。
Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity.
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
出版信息
Bioorg Med Chem Lett. 2010 Aug 1;20(15):4399-405. doi: 10.1016/j.bmcl.2010.06.062. Epub 2010 Jun 15.
We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models.
我们报告了一系列基于螺环吲哚酰胺优势结构的有效且选择性的 MC4R 激动剂，可用于肥胖的潜在治疗。在所使用的合成方法中，方法 C 允许类似物的快速合成。该系列化合物在 MC4R 上具有高活性，并且具有良好的啮齿动物药代动力学特征。化合物 1r（MK-0489）在小鼠模型中表现出 MC4R 介导的食物摄入和体重减少。化合物 1r 在为期 14 天的饮食诱导肥胖（DIO）大鼠模型中有效。
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