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

Abstract

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. © ECV · Editio Cantor Verlag, Aulendorf (Germany).