Synthesis and SAR of selective small molecule neuropeptide Y Y2 receptor antagonists

Bioorg Med Chem Lett. 2012 Jun 15;22(12):3916-20. doi: 10.1016/j.bmcl.2012.04.107. Epub 2012 Apr 30.

Abstract

Highly potent and selective small molecule neuropeptide Y Y2 receptor antagonists are reported. The systematic SAR exploration of a hit molecule N-(4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide, identified from HTS, led to the discovery of highly potent NPY Y2 antagonists 16 (CYM 9484) and 54 (CYM 9552) with IC(50) values of 19 nM and 12 nM respectively.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Obesity Agents / chemical synthesis*
  • Anti-Obesity Agents / pharmacology
  • Biological Assay
  • Cyclic AMP / analysis
  • High-Throughput Screening Assays
  • Humans
  • Mice
  • Molecular Weight
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacology
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / metabolism
  • Structure-Activity Relationship
  • Thiourea / analogs & derivatives*
  • Thiourea / chemical synthesis*
  • Thiourea / pharmacology

Substances

  • Anti-Obesity Agents
  • Piperidines
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor
  • Cyclic AMP
  • Thiourea