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Design and synthesis of sulfamoyl benzoic acid analogues with subnanomolar agonist activity specific to the LPA2 receptor.

ABSTRACT: 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.

SUBMITTER: Patil R

PROVIDER: S-EPMC4148159 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Design and synthesis of sulfamoyl benzoic acid analogues with subnanomolar agonist activity specific to the LPA2 receptor.

Patil Renukadevi R Fells James I JI Szabó Erzsébet E Lim Keng G KG Norman Derek D DD Balogh Andrea A Patil Shivaputra S Strobos Jur J Miller Duane D DD Tigyi Gábor J GJ

Journal of medicinal chemistry 20140812 16

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. ...[more]

PMID: 25100502

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