Synthesis and evaluation of new hydrazide derivatives as neuropeptide Y Y5 receptor antagonists for the treatment of obesity.
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).
Juanenea
Laura
L
Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiologia Aplicada (CIFA), Universidad de Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain.
Galiano
Silvia
S
Erviti
Oihana
O
Moreno
Antonio
A
Pérez
Silvia
S
Aldana
Ignacio
I
Monge
Antonio
A
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
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