110718-49-5Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of novel dual FFA1 (GPR40)/PPARδ agonists as potential anti-diabetic agents
Li, Zheng,Hu, Lijun,Wang, Xuekun,Zhou, Zongtao,Deng, Liming,Xu, Yawen,Zhang, Luyong
, (2019/09/12)
The free fatty acid receptor 1 (FFA1) and peroxisome proliferator-activated receptor δ (PPARδ) were considered as potential anti-diabetic targets, and the dual FFA1/PPARδ agonists might provide synergistic effect in insulin secretion and sensibility. Herein, we further develop dual agonists by screening 7 series of heterocycles, resulting in the discovery of compound 19 with considerable oral pharmacokinetic profile. Compound 19 exhibited a balanced potency between FFA1 and PPARδ, and high selectivity over PPARα and PPARγ. Moreover, compound 19 exerted improved glucose-lowering effects and insulin sensitivity in a dose-dependent manner, which might be attributed to its dual effects to simultaneously regulate insulin secretion and resistance. Our results extended the existing chemical space, and provided a potent tool compound 19.
