866944-99-2Relevant academic research and scientific papers
Potent and orally active non-peptide antagonists of the human melanocortin-4 receptor based on a series of trans-2-disubstituted cyclohexylpiperazines
Tucci, Fabio C.,White, Nicole S.,Markison, Stacy,Joppa, Margaret,Tran, Joe A.,Fleck, Beth A.,Madan, Ajay,Dyck, Brian P.,Parker, Jessica,Pontillo, Joseph,Arellano, L. Melissa,Marinkovic, Dragan,Jiang, Wanlong,Chen, Caroline W.,Gogas, Kathleen R.,Goodfellow, Val S.,Saunders, John,Foster, Alan C.,Chen, Chen
, p. 4389 - 4395 (2005)
The melanocortin-4 receptor (MC4R) plays an important role in the regulation of energy homeostasis. Recent studies have shown that blockade of the MC4R reverses tumor-induced weight loss in mice. Herein, we describe the synthesis and identification of potent and selective non-peptide antagonists of the human MC4R from a series of 2-ethoxycarbonylcyclohexyl-piperazines. Compound 12i was found to possess low nanomolar affinity for the MC4R, and exhibit oral bioavailability in rats. More importantly, when administered orally to mice (10 mg/kg), it led to statistically significant increases in food intake over a 24-h period.
