1390641-86-7Relevant academic research and scientific papers
Design, synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1
Yang, Jiaju,Gu, Enke,Yan, Ting,Shen, Daoming,Feng, Bainian,Tang, Chunlei
, p. 900 - 909 (2019)
Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK-875, AMG-837, and LY2881835. Among them, most promising compounds 7, 14, and 15 were obtained with EC50 values of 82, 79, and 88?nM, exhibiting a powerful agonistic activity compared to TAK-875 (95.1?nM). During Oral glucose tolerance test in normal mice, compound 7, 14, and 15 had significant glucose-lowering effect at the dose of 50?mg/kg. Furthermore, compound 15 (50?mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold.
Free fatty acid receptor 1 (FFA1/GPR40) agonists: Mesylpropoxy appendage lowers lipophilicity and improves ADME properties
Christiansen, Elisabeth,Due-Hansen, Maria E.,Urban, Christian,Grundmann, Manuel,Schr?der, Ralf,Hudson, Brian D.,Milligan, Graeme,Cawthorne, Michael A.,Kostenis, Evi,Kassack, Matthias U.,Ulven, Trond
supporting information; experimental part, p. 6624 - 6628 (2012/09/21)
FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metabolic stability while preserving potency, resulting in discovery of the potent FFA1 agonist 13.
