Discovery of diacylphloroglucinols as a new class of GPR40 (FFAR1) agonists

Abstract In this letter, we report discovery of diacylphloroglucinol compounds as a new class of GPR40 (FFAR1) agonists. Several diacylphloroglucinols with varying length of acyl functionality and substitution on aromatic hydroxyls were synthesized and evaluated for GPR40 agonism using functional calcium-flux assay. Out of 17 compounds evaluated, 14 , 17 , 19 and 25 exhibited good GPR40 agonistic activity with EC 50 values ranging from 0.07 to 8 μM (pEC 50 7.12–5.09), respectively, with maximal agonistic response of 84–102%.