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N-Arylated-Lactam-Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation
Wu, Xiaowei1; Zhang, Fu-Yu1; Zhu, Jingjing1,2; Song, Chengcheng1,2; Xiong, De-Cai1; Zhou, Yifa2; Cui, Yuxin1; Ye, Xin-Shan1
关键词Arylation Crosscoupling Iminosugars Immunology Lactams
刊名CHEMISTRY-AN ASIAN JOURNAL
2014-08-01
DOI10.1002/asia.201400023
9期:8页:2260-2271
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary
资助者Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Beijing Higher Education Young Elite Teacher Project ; Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Beijing Higher Education Young Elite Teacher Project
研究领域[WOS]Chemistry
关键词[WOS]GLYCOSIDASE INHIBITORS ; ANALOG INHIBITORS ; IFN-GAMMA ; DERIVATIVES ; HALIDES ; DESIGN ; GALACTOFURANOSE ; BIOSYNTHESIS ; SWAINSONINE ; AMIDATION
英文摘要

We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of ′hit′ compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21h, 21k, 21n, 21 t, and 21 x with improved activities (IC50=12-30 mm) and low Jurkat cytotoxicities (IC50>100 mm). These new compounds also inhibited the secretion of IFN-gamma and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity.

语种英语
所属项目编号2012CB822100 ; 2013CB910700 ; 91213301 ; 21232002
资助者Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Beijing Higher Education Young Elite Teacher Project ; Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Beijing Higher Education Young Elite Teacher Project
WOS记录号WOS:000342675900039
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56519
专题北京大学药学院
作者单位1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.NE Normal Univ, Sch Life Sci, Changchun 130024, Peoples R China
推荐引用方式
GB/T 7714
Wu, Xiaowei,Zhang, Fu-Yu,Zhu, Jingjing,et al. N-Arylated-Lactam-Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation[J]. CHEMISTRY-AN ASIAN JOURNAL,2014,9(8):2260-2271.
APA Wu, Xiaowei.,Zhang, Fu-Yu.,Zhu, Jingjing.,Song, Chengcheng.,Xiong, De-Cai.,...&Ye, Xin-Shan.(2014).N-Arylated-Lactam-Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation.CHEMISTRY-AN ASIAN JOURNAL,9(8),2260-2271.
MLA Wu, Xiaowei,et al."N-Arylated-Lactam-Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation".CHEMISTRY-AN ASIAN JOURNAL 9.8(2014):2260-2271.
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