title: Identification and SAR of Glycine Benzamides as Potent Agonists for the GPR139 Receptor.
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.
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Curt A
authors.initials: CA
authors.lastname: Dvorak
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Coate
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Diane
authors.initials: D
authors.lastname: Nepomuceno
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Wennerholm
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Chester
authors.initials: C
authors.lastname: Kuei
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Lord
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: David
authors.initials: D
authors.lastname: Woody
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonaventure
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Changlu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lovenberg
authors.affiliation: Janssen Research & Development, LLC , San Diego, California 92121, United States.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
keywords: GPR139; Orphan receptors; agonists; glycine amides