Novel orally active NPY Y5 receptor antagonists: Synthesis and structure-activity relationship of spiroindoline class compounds

Bioorg Med Chem. 2009 Jul 15;17(14):5015-26. doi: 10.1016/j.bmc.2009.05.064. Epub 2009 Jun 2.

Abstract

Spiroindoline urea derivatives, designed to act as NPY Y5 receptor antagonists, were synthesized and their structure-activity relationships were investigated. Of these derivatives, compound 3a showed good Y5 binding affinity with favorable pharmacokinetic properties. Compound 3a significantly inhibited bPP Y5 agonist-induced food intake in rats, and suppressed body weight gain in DIO mice.

MeSH terms

  • Animals
  • Anti-Obesity Agents / chemical synthesis
  • Anti-Obesity Agents / chemistry*
  • Anti-Obesity Agents / pharmacokinetics
  • Anti-Obesity Agents / pharmacology*
  • Biological Availability
  • Body Weight / drug effects
  • Eating / drug effects
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide Y / agonists
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / metabolism*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacokinetics
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Obesity Agents
  • Indoles
  • Receptors, Neuropeptide Y
  • Spiro Compounds
  • neuropeptide Y5 receptor
  • indoline