A potent and selective nonpeptide antagonist of the melanocortin-4 receptor induces food intake in satiated mice

被引：24
|
作者：
Pontillo, J
Tran, JA
Markison, S
Joppa, M
Fleck, BA
Marinkovic, D
Arellano, M
Tucci, FC
Lanier, M
Nelson, J
Saunders, J
Hoare, SRJ
Foster, AC
Chen, C
机构：
[1] Neurocrine Biosci Inc, Dept Med Chem, San Diego, CA 92130 USA
[2] Neurocrine Biosci Inc, Dept Pharmacol, San Diego, CA 92130 USA
[3] Neurocrine Biosci Inc, Dept Neurosci, San Diego, CA 92130 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 10期
关键词：
melanocortin-4; antagonist; piperazinebenzylamine; food intake;
D O I：
10.1016/j.bmcl.2005.03.053
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Optimization on a series of piperazinebenzylamines resulted in analogues with low nanomolar binding at the human MC4 receptor but weak affinity (K-i > 500 nM) at the MC3 receptor. Compound 14c was identified to be a potent MC4R antagonist (K-i = 3.2 nM) with a selectivity of 240-fold over MC3R. It proved to be an insurmountable antagonist in a cAMP assay. Compound 14c potently stimulated food intake in satiated mice when given by intracerebroventricular administration. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2541 / 2546
页数：6
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