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

  • Bioorg Med Chem Lett. 2008 Dec 15;18(24):6357-61. doi: 10.1016/j.bmcl.2008.10.085.
Sandip B Bharate  1 ,  Atish Rodge ,  Rajendra K Joshi ,  Jaspreet Kaur ,  Shaila Srinivasan ,  S Senthil Kumar ,  Asha Kulkarni-Almeida ,  Sarala Balachandran ,  Arun Balakrishnan ,  Ram A Vishwakarma
Affiliations
  • 1. Department of Medicinal Chemistry, Piramal Life Sciences Limited, 1 Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400063, India.
PMID: 18993064 DOI: 10.1016/j.bmcl.2008.10.085
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 microM (pEC(50) 7.12-5.09), respectively, with maximal agonistic response of 84-102%.