Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1377166 | Bioorganic & Medicinal Chemistry Letters | 2007 | 7 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 20f-1 and 20f-2 displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-compound 20f-1 possessed a Ki of 11 nM and an EC50 of 24 nM, while its 3R,4S-isomer 20f-2 exhibited a Ki of 8.6 and an IC50 of 65 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 20f-1 also demonstrated efficacy in diet-induced obese rats.
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Related Topics
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Authors
Wanlong Jiang, Joe A. Tran, Fabio C. Tucci, Beth A. Fleck, Sam R. Hoare, Stacy Markison, Jenny Wen, Caroline W. Chen, Dragan Marinkovic, Melissa Arellano, Alan C. Foster, Chen Chen,