Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1376895 | Bioorganic & Medicinal Chemistry Letters | 2008 | 8 Pages |
Abstract
A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a Ki of 1.0 nM and an EC50 of 3.8 nM, while its 3R,4S-isomer 13b-2 exhibited a Ki of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Chen Chen, Wanlong Jiang, Joe A. Tran, Fabio C. Tucci, Beth A. Fleck, Stacy Markison, Jenny Wen, Ajay Madan, Sam R. Hoare, Alan C. Foster, Dragan Marinkovic, Caroline W. Chen, Melissa Arellano, John Saunders,