|
|||||
|
|
Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity |
|
| Authors: | Shuwen He Zhixiong Ye Peter H. Dobbelaar Iyassu K. Sebhat Liangqin Guo Jian Liu Tianying Jian Yingjie Lai Christopher L. Franklin Raman K. Bakshi James P. Dellureficio Qingmei Hong David H. Weinberg Tanya MacNeil Rui Tang Alison M. Strack Constantin Tamvakopoulos Qianping Peng Randy R. Miller Ralph A. Stearns Ravi P. Nargund |
| Affiliation: | 1. Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA;2. Department of Metabolic Disorders, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA;3. Department of Pharmacology, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA;4. Department of Drug Metabolism, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA |
| 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. |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ | |