Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor |
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| Authors: | Pontillo Joseph Tran Joseph A Fleck Beth A Marinkovic Dragan Arellano Melissa Tucci Fabio C Lanier Marion Nelson Jodie Parker Jessica Saunders John Murphy Brian Foster Alan C Chen Chen |
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| Institution: | Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA. |
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| Abstract: | SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and 11l, which had K(i) values of 21, 14, and 15 nM, respectively, possessed low efficacy in cAMP stimulation ( approximately 15% of alpha-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of alpha-MSH-stimulated cAMP release in a dose-dependent manner (11l, IC(50)=36 nM). |
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