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

Arzneimittelforschung. 2005;55(2):81-5. doi: 10.1055/s-0031-1296827.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Obesity Agents / chemical synthesis*
  • Anti-Obesity Agents / therapeutic use*
  • Humans
  • Hydrazines / chemical synthesis*
  • Hydrazines / therapeutic use*
  • Indicators and Reagents
  • Obesity / drug therapy*
  • Pyridines / chemical synthesis*
  • Pyridines / therapeutic use*
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis

Substances

  • Anti-Obesity Agents
  • Hydrazines
  • Indicators and Reagents
  • Pyridines
  • Receptors, Neuropeptide Y
  • Sulfonamides
  • neuropeptide Y5 receptor