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Published on: October 22, 2015
Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity
Shuwen He1, Zhixiong Ye, Peter H Dobbelaar
1Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. shuwen_he@merck.com
Abstract:
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.
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