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Updated: Aug 9, 2025

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Structure-based design of novel melanin-concentrating hormone receptor-1 ligands based on saturated
Mohamed A Helal1, Amar G Chittiboyina2, Mitchell A Avery3
1University of Science and Technology, Biomedical Sciences Program, Zewail City of Science and Technology, October Gardens, 6th of October, Giza 12578, Egypt; Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
Abstract:
Melanin Concentrating Hormone (MCH) receptor is a G protein-coupled receptor (GPCR) with two subtypes R1 and R2. MCH-R1 is involved in the control of energy homeostasis, feeding behavior and body weight. Many studies have proved that administration of MCH-R1 antagonists significantly reduces food intake and causes weight loss in animal models. Herein, we report the optimization of our previously reported virtual screening hits into novel MCH-R1 ligands with chiral aliphatic nitrogen-containing scaffolds. The activity was improved from the micromolar range of the initial leads to 7 nM. We also disclose the first MCH-R1 ligands based on a diazaspiro[4.5]decane nucleus with sub-micromolar activity. A potent MCH-R1 antagonist with acceptable pharmacokinetic profile could represent a new hope for the management of obesity.
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