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

Renukadevi Patil; James I Fells; Erzsébet Szabó; Keng G Lim; Derek D Norman; Andrea Balogh; Shivaputra Patil; Jur Strobos; Duane D Miller; Gábor J Tigyi

doi:10.1021/jm5007116

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

J Med Chem. 2014 Aug 28;57(16):7136-40. doi: 10.1021/jm5007116. Epub 2014 Aug 12.

Authors

Renukadevi Patil¹, James I Fells, Erzsébet Szabó, Keng G Lim, Derek D Norman, Andrea Balogh, Shivaputra Patil, Jur Strobos, Duane D Miller, Gábor J Tigyi

Affiliation

¹ Departments of Pharmaceutical Sciences and ‡Physiology, The University of Tennessee Health Science Center , Memphis, Tennessee 894 Union Avenue 38163 United States.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Benzoates / chemistry*
Binding Sites
Chemistry Techniques, Synthetic
Drug Design
Drug Evaluation, Preclinical / methods
Humans
Molecular Docking Simulation
Receptors, Lysophosphatidic Acid / agonists*
Receptors, Lysophosphatidic Acid / chemistry
Receptors, Lysophosphatidic Acid / metabolism
Structure-Activity Relationship

Substances

Benzoates
Receptors, Lysophosphatidic Acid
carzenide

Abstract

Publication types

MeSH terms

Substances

Grants and funding