新型嘧啶二酮衍生物作为二肽基肽酶-4抑制剂的设计、合成及生物学评价
Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors.
作者信息
Li Ning, Wang Li-Jun, Jiang Bo, Guo Shu-Ju, Li Xiang-Qian, Chen Xue-Chun, Luo Jiao, Li Chao, Wang Yi, Shi Da-Yong
机构信息
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China; University of Chinese Academy of Sciences, Beijing 100049, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China.
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China.
出版信息
Bioorg Med Chem Lett. 2018 Jul 1;28(12):2131-2135. doi: 10.1016/j.bmcl.2018.05.022. Epub 2018 May 16.
A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC values of 64.47 nM, 188.7 nM and 65.36 nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure-activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes.
设计并评估了一系列新型嘧啶二酮衍生物的体外二肽基肽酶-4（DPP-4）抑制活性和体内抗高血糖功效。其中，代表性化合物11、15和16对DPP-4表现出优异的抑制活性，IC值分别为64.47 nM、188.7 nM和65.36 nM。进一步研究表明，化合物11在体内具有显著的降血糖作用。讨论了这些嘧啶二酮衍生物的构效关系，这将有助于开发新型DPP-4抑制剂用于治疗2型糖尿病。
Zotero 插件