Identification of piperazine-bisamide GHSR antagonists for the treatment of obesity

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1758-62. doi: 10.1016/j.bmcl.2010.01.043. Epub 2010 Jan 20.

Abstract

Piperazine-bisamide analogs were discovered as partial agonists of human growth hormone secretagogue receptor (GHSR) in a high throughput screen. The partial agonists were optimized for potency and converted into antagonists through structure-activity relationship (SAR) studies. The efforts also led to the identification of potent antagonist with favorable PK profile suitable as a tool compound for in vivo studies.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / therapeutic use
  • Animals
  • Anti-Obesity Agents / chemical synthesis
  • Anti-Obesity Agents / chemistry*
  • Anti-Obesity Agents / therapeutic use
  • High-Throughput Screening Assays
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / therapeutic use
  • Obesity / drug therapy
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / therapeutic use
  • Rats
  • Receptors, Ghrelin / antagonists & inhibitors*
  • Receptors, Ghrelin / metabolism
  • Structure-Activity Relationship

Substances

  • Amides
  • Anti-Obesity Agents
  • Indoles
  • Piperazines
  • Receptors, Ghrelin