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1. Synthesis and evaluation of new hydrazide derivatives as neuropeptide Y Y5 receptor antagonists for the treatment of obesity.

Author

Juanenea L, Galiano S, Erviti O, Moreno A, Pérez S, Aldana I, and Monge A

Subjects
Animals, Anti-Obesity Agents pharmacology, Binding, Competitive drug effects, Cell Line, Humans, Hydrazines pharmacology, Inhibitory Concentration 50, Obesity drug therapy, Structure-Activity Relationship, Sulfonamides pharmacology, Hydrazines chemical synthesis, Neuropeptide Y metabolism, Receptors, Neuropeptide Y antagonists & inhibitors, Sulfonamides chemical synthesis
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).

Published
2004
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