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

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.

Optimization of the initial growth hormone secretagogue receptor (GHSR) partial agonist 1a provided the antagonistic tool compound 8b that featured with improved potency, complete elimination of the partial agonist activity, and suitable PK profiles.Figure optionsDownload as PowerPoint slide