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

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• 作者：Curt A. Dvorak ; Heather Coate ; Diane Nepomuceno ; Michelle Wennerholm ; Chester Kuei ; Brian Lord ; David Woody ; Pascal Bonaventure ; Changlu Liu ; Timothy Lovenberg ; Nicholas I. Carruthers
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：September 10, 2015
• 年：2015
• 卷：6
• 期：9
• 页码：1015-1018
• 全文大小：215K
• ISSN：1948-5875

文摘

A focused high throughput screening for GPR139 was completed for a select 100K compounds, and new agonist leads were identified. Subsequent analysis and structure鈥揳ctivity 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鈥揵rain barrier and have good drug-like properties amenable for oral dosing in rat.