Author/Authors :
Wanlong Jiang، نويسنده , , Fabio C. Tucci، نويسنده , , Joe A. Tran، نويسنده , , Beth A. Fleck، نويسنده , , Jenny Wen، نويسنده , , Stacy Markison، نويسنده , , Dragan Marinkovic، نويسنده , , Caroline W. Chen، نويسنده , , Melissa Arellano، نويسنده , , Sam R. Hoare، نويسنده , , Michael Johns، نويسنده , , Alan C. Foster، نويسنده , , John Saunders، نويسنده , , Chen Chen، نويسنده ,
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.
Keywords :
melanocortin-4 receptor , CYP3A4 enzyme , cachexia , Lipophilicity , Pharmacokinetics , Antagonist , Pyrrolidinone
