Identification of novel multitargeted PPARa/?/d pan agonists by core hopping of rosiglitazone

Wang, Xue-Jiao; Zhang, Jun; Wang, Shu-Qing; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

In recent years, some novel PPARs concepts appeared in the antidiabetic drug research area, such as multitargeted cooperative PPARα/γ dual agonists and PPARα/γ/δ pan agonists. These multitargeted agonists could cooperatively improve glucose and lipid metabolism. They could not only effectively control blood sugar but also reduce the content of triglyceride, free fatty acid, and low-density lipoprotein, as well as increase high-density lipoprotein concentration, thus having a preventive effect on cardiovascular complications of type 2 diabetes patients. Some of these multitargeted PPARs agonists have entered clinical trials and represent promising PPARs drug research. [11] [12] [13] The pharmacophore of PPARs agonists consists of the polar head, linker, and hydrophobic tail. The polar head of PPARs agonists could form a hydrogen bond with Tyr residue at the AF-2 region, producing a transactivation effect. The hydrophobic