Bharate Sandip B, Rodge Atish, Joshi Rajendra K, Kaur Jaspreet, Srinivasan Shaila, Kumar S Senthil, Kulkarni-Almeida Asha, Balachandran Sarala, Balakrishnan Arun, Vishwakarma Ram A
Department of Medicinal Chemistry, Piramal Life Sciences Limited, 1 Nirlon Complex, Off Western Express Highway, Goregaon (E), Mumbai 400063, India.
Bioorg Med Chem Lett. 2008 Dec 15;18(24):6357-61. doi: 10.1016/j.bmcl.2008.10.085. Epub 2008 Nov 1.
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%.
在本信函中，我们报告发现二酰基间苯三酚化合物是一类新型的GPR40（游离脂肪酸受体1）激动剂。合成了几种具有不同酰基官能团长度和芳族羟基取代的二酰基间苯三酚，并使用功能性钙流测定法评估其对GPR40的激动作用。在评估的17种化合物中，14、17、19和25表现出良好的GPR40激动活性，其半数有效浓度（EC50）值分别为0.07至8微摩尔（pEC50为7.12 - 5.09），最大激动反应为84 - 102%。
