Design and Synthesis of Sulfamoyl Benzoic Acid Analogues with Subnanomolar Agonist Activity Specific to the LPA(2) Receptor

[Image: see text] Lysophosphatidic acid (LPA) is a growth factor-like mediator and a ligand for multiple GPCR. The LPA(2) 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 LPA(2...

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Detalles Bibliográficos
Autores principales: Patil, Renukadevi, Fells, James I., Szabó, Erzsébet, Lim, Keng G., Norman, Derek D., Balogh, Andrea, Patil, Shivaputra, Strobos, Jur, Miller, Duane D., Tigyi, Gábor J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148159/
https://www.ncbi.nlm.nih.gov/pubmed/25100502
http://dx.doi.org/10.1021/jm5007116
Descripción
Sumario:[Image: see text] Lysophosphatidic acid (LPA) is a growth factor-like mediator and a ligand for multiple GPCR. The LPA(2) 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 LPA(2), some with subnanomolar activity. We developed an experimental SAR that is supported and rationalized by computational docking analysis of the SBA compounds into the LPA(2) ligand-binding pocket.

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