n-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3-4-difluorobenzamide-hydrochloride has been researched along with Obesity* in 2 studies
2 other study(ies) available for n-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3-4-difluorobenzamide-hydrochloride and Obesity
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Identification of a new small molecule chemotype of Melanin Concentrating Hormone Receptor-1 antagonists using pharmacophore-based virtual screening.
MCH receptor is a G protein-coupled receptor with two subtypes R1 and R2. Many studies have demonstrated the role of MCH-R1 in feeding and energy homeostasis. It has been proven that oral administration of small molecule MCH-R1 antagonists significantly reduces food intake and causes a dose-dependent weight loss. In this study, two ligand-based pharmacophores were developed and validated based on recently published MCH-R1 antagonists with diverse structures. Successful pharmacophores had one hydrogen bond acceptor, one positive ionizable, one ring aromatic and two or three hydrophobic groups. These 3D-QSAR models were used for virtual screening of the ZINC chemical database resulting in the identification of nine compounds with more than 50% displacement of radiolabeled MCH at a 20 μM concentration. Moreover, four of these compounds showed antagonistic activities in Aequorin functional assay, including MH-3 which is the first MCH-R1 antagonist based on a diazaspiro[4.5]decane scaffold. The most active compounds were also docked into our previously published MCH-R1 homology model to gain insights into their binding determinants. These compounds could represent a viable starting scaffold for the design of potent MCH-R1 antagonists with improved pharmacokinetic properties as an effective treatment for obesity. Topics: Anti-Obesity Agents; Humans; Obesity; Receptors, Pituitary Hormone; Structure-Activity Relationship | 2019 |
Discovery of bicycloalkyl urea melanin concentrating hormone receptor antagonists: orally efficacious antiobesity therapeutics.
Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 antagonists that exhibit in vivo efficacy in rodent obesity models. Topics: Administration, Oral; Animals; Anti-Obesity Agents; Biological Availability; Brain; Bridged Bicyclo Compounds; Cycloheptanes; Cyclohexanes; Eating; Mice; Obesity; Rats; Receptors, Pituitary Hormone; Receptors, Somatostatin; Urea | 2005 |