The discovery and synthesis of JNJ 31020028, a small molecule antagonist of the Neuropeptide Y Y₂ receptor

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5552-6. doi: 10.1016/j.bmcl.2011.06.136. Epub 2011 Jul 18.

Abstract

A series of small molecules based on a chemotype identified from our compound collection were synthesized and tested for binding affinity (IC(50)) at the human Neuropeptide Y Y(2) receptor (NPY Y(2)). Six of the 23 analogs tested possessed an NPY Y(2) IC(50) ≤ 15 nM. One member of this series, JNJ 31020028, is a selective, high affinity, receptor antagonist existing as a racemic mixture. As such a synthetic route to the desired enantiomer was designed starting from commercially available (S)-(+)-mandelic acid.

MeSH terms

  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Chemistry Techniques, Synthetic
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Molecular Structure
  • Molecular Weight
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Benzamides
  • JNJ-31020028
  • Piperazines
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor