Design and Synthesis of Sulfamoyl Benzoic Acid Analogues with Subnanomolar Agonist Activity Specific to the LPA2 Receptor

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• 作者：Renukadevi Patil ; James I. Fells ; Erzs茅bet Szab贸 ; Keng G. Lim ; Derek D. Norman ; Andrea Balogh ; Shivaputra Patil ; Jur Strobos ; Duane D. Miller ; G谩bor J. Tigyi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：August 28, 2014
• 年：2014
• 卷：57
• 期：16
• 页码：7136-7140
• 全文大小：331K
• ISSN：1520-4804

文摘

Lysophosphatidic acid (LPA) is a growth factor-like mediator and a ligand for multiple GPCR. The LPA₂ GPCR mediates antiapoptotic and mucosal barrier-protective effects in the gut. We synthesized sulfamoyl benzoic acid (SBA) analogues that are the first specific agonists of LPA₂, some with subnanomolar activity. We developed an experimental SAR that is supported and rationalized by computational docking analysis of the SBA compounds into the LPA₂ ligand-binding pocket.