Pyrrolidinones as potent functional antagonists of the human melanocortin-4 receptor

https://doi.org/10.1016/j.bmcl.2007.07.097Get rights and content

Abstract

A series of pyrrolidinones derived from phenylalaninepiperazines were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor. In addition to their high binding affinities, these compounds displayed high functional potencies. 12a had a Ki of 0.94 nM in binding and IC50 of 21 nM in functional activity. 12a also demonstrated efficacy in a mouse cachexia model.

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Acknowledgment

The authors thank Dr. Daniel Marks of Oregon Health & Science University for his help in performing the mouse cachexia study.

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