Compounds > n-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3-4-difluorobenzamide-hydrochloride

n-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3-4-difluorobenzamide-hydrochloride and Obesity

n-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3-4-difluorobenzamide-hydrochloride has been researched along with Obesity* in 2 studies

Other Studies

2 other study(ies) available for n-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3-4-difluorobenzamide-hydrochloride and Obesity

Article	Year
Identification of a new small molecule chemotype of Melanin Concentrating Hormone Receptor-1 antagonists using pharmacophore-based virtual screening. Bioorganic & medicinal chemistry letters, 2019, 12-15, Volume: 29, Issue:24 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. Journal of medicinal chemistry, 2005, Apr-07, Volume: 48, Issue:7 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

Article

Year

Identification of a new small molecule chemotype of Melanin Concentrating Hormone Receptor-1 antagonists using pharmacophore-based virtual screening.

Bioorganic & medicinal chemistry letters, 2019, 12-15, Volume: 29, Issue:24

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.

Journal of medicinal chemistry, 2005, Apr-07, Volume: 48, Issue:7

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