Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor

  • ACS Med Chem Lett. 2015 Jul 20;6(9):1015-8. doi: 10.1021/acsmedchemlett.5b00247.
Curt A Dvorak  1 ,  Heather Coate  1 ,  Diane Nepomuceno  1 ,  Michelle Wennerholm  1 ,  Chester Kuei  1 ,  Brian Lord  1 ,  David Woody  1 ,  Pascal Bonaventure  1 ,  Changlu Liu  1 ,  Timothy Lovenberg  1 ,  Nicholas I Carruthers  1
Affiliations
  • 1. Janssen Research & Development, LLC , San Diego, California 92121, United States.
PMID: 26396690 DOI: 10.1021/acsmedchemlett.5b00247
Abstract

A focused high throughput screening for GPR139 was completed for a select 100K compounds, and new agonist leads were identified. Subsequent analysis and structure-activity relationship studies identified (S)-3-chloro-N-(2-oxo-2-((1-phenylethyl)amino)ethyl)benzamide 7c as a potent and selective agonist of hGPR139 with an EC50 = 16 nM. The compound was found to cross the blood-brain barrier and have good drug-like properties amenable for oral dosing in rat.

Keywords
GPR139; Orphan receptors; agonists; glycine amides.
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