discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-n-phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors：（发现2 -((4 6-dimethylpyrimidin-2-yl)含硫的)-n-phenylacetamide衍生品作为新的有效和选择性人类sirtuin 2抑制剂）.pdfVIP

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discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-n-phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors：（发现2 -((4 6-dimethylpyrimidin-2-yl)含硫的)-n-phenylacetamide衍生品作为新的有效和选择性人类sirtuin 2抑制剂）.pdf

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discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-n-phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors：（发现2 -((4 6-dimethylpyrimidin-2-yl)含硫的)-n-phenylacetamide衍生品作为新的有效和选择性人类sirtuin 2抑制剂）

European Journal of Medicinal Chemistry 134 (2017) 230e241 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier .com/locate/ejmech Research paper Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-N- phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors Lingling Yang a, *, Xiaobo Ma b, Chen Yuan a, Yanying He a, Ling Li a, Sha Fang a, Wei Xia a, Tao He b, Shan Qian a, Zhihong Xu b, Guobo Li c, Zhouyu Wang b, ** a College of Food and Bioengineering, Xihua University, Sichuan 610039, China b College of Science, Xihua University, Sichuan 610039, China c Key Laboratory of Drug Targeting, Drug Delivery System of Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China a r t i c l e i n f o a b s t r a c t Article history: Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, Received 28 October 2016 autophagy, immune and inﬂammatory responses. Dysregulation of SIRT2 was considered as a main Received in revised form aspect contributing to several human diseases, including cancer. Development of new potent and se- 1 April 2017 lective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related Accepted 6 April 2017 diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl) Available online 12 April 2017