discovery of new syk inhibitors through structure-based virtual screening：（新发现的麦克米兰抑制剂通过基于结构的虚拟筛选）.pdfVIP

Bioorganic Medicinal Chemistry Letters 27 (2017) 1776–1779 Contents lists available at ScienceDirect Bioorganic Medicinal Chemistry Letters journal homepage: www.else /locate/bmcl Discovery of new Syk inhibitors through structure-based virtual screening Yahui Huang a,e, Youjun Zhang b,e, Kexin Fan c, Guoqiang Dong a, Bohua Li c, Wannian Zhang a,⇑, Jian Li d,⇑, Chunquan Sheng a,⇑ a School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People’s Republic of China b Department of Naval Health Service and Medical Equipment, Faculty of Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People’s Republic of China c International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People’s Republic of China d School of Pharmacy, East China University of Science Technology, 130 Meilong Road, Shanghai 200237, People’s Republic of China a r t i c l e i n f o a b s t r a c t Article history: Spleen tyrosine kinase (Syk) is an attractive target for the discovery of new treatments for inflammatory Received 19 January 2017 and autoimmune disorders. Structure-based virtual screening was performed for identifying novel scaf- Revised 22 February 2017 folds of Syk inhibitors. A total of 16 hits were discovered in the enzyme assay and 8 compounds had an Accepted 23 February 2017 IC50 value lower than 10 lM. In particular, compound 11 (IC50 = 3.2 lM) was active in the cellular Syk Available online 24 February 2017