Novel human neuropeptide Y Y5 receptor antagonists for the treatment of obesity. Synthesis and biological evaluation of pyridine hydrazide derivatives.

A series of new pyridine hydrazide derivatives with high and selective antagonist activity at the human neuropeptide Y Y5 receptor were developed. Introduction of electron-withdrawing groups into the arylsulfonamide rest, together with the 3-pyridyl analogue in the hydrazide moiety, led to a significant improvement of potency and solubility, affording trans-N-(4-[N'-(pyridine-3-carbonyl)hydrazino-carbonyl]cyclohexylmethyl)-2,4-dichloro-benzenesulfonamide (14), which binds to the hY5 receptor with an IC50 value of 7.44 nmol/L.