Design and synthesis of novel hydantoin-containing melanin-concentrating hormone receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 13; pp. 3754 - 3759
• Main Authors: Balavoine, Fabrice, Malabre, Patrice, Alleaume, Thierry, Rey, Astrid, Cherfils, Valérie, Jeanneton, Olivier, Seigneurin-Venin, Sophie, Revah, Frédéric
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2007; Elsevier
• Subjects: Animals; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Depression; Depression - drug therapy; Disease Models, Animal; Drug Design; Feeding; Feeding Behavior - drug effects; Hormones. Endocrine system; Hydantoin; Hydantoins - chemistry; Kinetics; MCHR-1 antagonists; Medical sciences; Melanin-concentrating hormone; Melanins - chemistry; Models, Biological; Models, Chemical; Models, Molecular; Neuropharmacology; Obesity; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Pituitary Hormone - antagonists & inhibitors; Receptors, Pituitary Hormone - chemistry; Receptors, Somatostatin - antagonists & inhibitors; Structure-Activity Relationship; Obesity; Depression; Melanin-concentrating hormone; MCHR-1 antagonists; Hydantoin; Feeding; Five membered ring; Intraperitoneal administration; Nitrogen heterocycle; Psychotropic; Pyrrolidine derivatives; Structure activity relation; Melanin concentrating hormone; Antidepressant agent; Antagonist; Chemical synthesis; Nutritional status; Biological receptor; Mood disorder; Absorption Distribution Metabolisme Excretion; Rodentia; Nutrition disorder; Benzene derivatives; Prediction; Hydantoins; In vitro; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Tertiary amine; Affinity; Anorectic; Pharmacokinetics; Hormonal receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.04.012

We report here new chemical series acting as antagonists of melanin-concentrating hormone receptor 1 (MCHR-1). Synthesis and structure–activity relationships are described leading to the identification of compounds with optimized in vitro pharmacological and in vitro ADME profiles. In vivo activity has been demonstrated in animal models of food intake and depression. We report here new chemical series acting as antagonists of melanin-concentrating hormone receptor 1 (MCHR-1). Synthesis and structure–activity relationships are described leading to the identification of compounds with optimized in vitro pharmacological and in vitro ADME profiles. In vivo activity has been demonstrated in animal models of food intake and depression.