Design and synthesis of novel pyrimido[5,4-d]pyrimidine derivatives as GPR119 agonist for treatment of type 2 diabetes |
| |
| Authors: | Yuanying Fang Jun Xu Zhifeng Li Zunhua Yang Lijuan Xiong Yi Jin Qi Wang Saisai Xie Wufu Zhu Sheng Chang |
| |
| Affiliation: | 1. National Engineering Research Center for Manufacturing Technology of TCM Solid Preparation, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China;2. College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;3. College of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China;4. College of Pharmacy, Jilin Medical University, Jilin 132013, China |
| |
| Abstract: | We described the discovery and optimization of a novel series of pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119) agonists against type 2 diabetes. Most designed compounds displayed significant GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly potent agonistic activities with single digit EC50 values (2.2?nM and 8.1?nM, respectively). Therefore, 15a and 21e were evaluated for their oral glucose tolerance test (oGTT) in C57BL/6N mice. Compound 15a reduced the blood glucose area of under curve from 0 to 2?h (AUC0–2h) to 13.5% at the dose of 15?mg/kg comparing with Metformin reduced 18% of AUC0–2h at the dose of 300?mg/kg. |
| |
| Keywords: | GPR119 agonist Type 2 diabetes oGTT |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
