title: Synthesis and evaluation of new hydrazide derivatives as neuropeptide Y Y5 receptor antagonists for the treatment of obesity.
abstract: NPY is the most potent orexigenic agent known to man, with NPY Y1 and NPY Y5 being the receptor subtypes that are most likely responsible for centrally-mediated NPY-induced feeding responses. Based on the aforementioned, novel hydrazide derivatives were prepared for the purpose of searching new NPY Y5 receptor antagonists. Many of the compounds exhibited nanomolar binding affinity for this receptor, affording trans-N-(4-[N'-(3,4-dichlorophenyl)hydrazinocarbonyl]cyclohexylmethyl)-4-fluorobenzenesulfonamide, which showed the best activity (IC(50)=0.43nM).
authors.affiliation: Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiologia Aplicada (CIFA), Universidad de Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Juanenea
authors.forename: Silvia
authors.initials: S
authors.lastname: Galiano
authors.forename: Oihana
authors.initials: O
authors.lastname: Erviti
authors.forename: Antonio
authors.initials: A
authors.lastname: Moreno
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009478:Neuropeptide Y / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D019440:Anti-Obesity Agents; D006834:Hydrazines; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D013449:Sulfonamides; C100568:neuropeptide Y5 receptor; C502720:trans-N-(4-(N'-(3,4-dichlorophenyl)hydrazinocarbonyl)cyclohexylmethyl)-4-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides