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

被引：34

作者：

Bharate, Sandip B. ^{[1
]}

Rodge, Atish ^{[1
]}

Joshi, Rajendra K. ^{[3
]}

Kaur, Jaspreet ^{[3
]}

Srinivasan, Shaila ^{[3
]}

Kumar, S. Senthil ^{[2
]}

Kulkarni-Almeida, Asha ^{[2
]}

Balachandran, Sarala ^{[1
]}

Balakrishnan, Arun ^{[2
]}

Vishwakarma, Ram A. ^{[1
]}

机构：

[1] Piramal Life Sci Ltd, Dept Med Chem, Bombay 400063, Maharashtra, India

[2] Piramal Life Sci Ltd, Dept Screening & Biotechnol, Bombay 400063, Maharashtra, India

[3] Piramal Life Sci Ltd, Dept Pharmacol, Bombay 400063, Maharashtra, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 24期

关键词：

Diacylphloroglucinols; FFAR1; agonist; GPR40; Type-2; diabetes;

D O I：

10.1016/j.bmcl.2008.10.085

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M (pEC(50) 7.12-5.09), respectively, with maximal agonistic response of 84-102%. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6357 / 6361

页数：5

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