文献类型：期刊文献

中文题名：Design and Synthesis of a Series of Novel Macrocycle Janus Kinase 2 Inhibitors

作者：Yanling Wang[1];Huan Ge[1];Disha Wang[1];Huan He[1];Lu Li[1];Yanyan Diao[1];Zihao Shen[1];Lili Zhu[1];Shiliang Li[1];Zhenjiang Zhao[1];Honglin Li[1]

机构：[1]Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,130 Meilong Road,Shanghai 200237,China

年份：2019

卷号：37

期号：12

起止页码：1259

中文期刊名：Chinese Journal of Chemistry

外文期刊名：中国化学（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2019_2020】；

基金：The research is supported in part by the National Key Research and Development Program(Grant No.2016YFA0502304);the National Natural Science Foundation of China(Grant No.81825020);the National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(No.2018ZX09711002);the Fundamental Research Funds for the Central Universities;Honglin Li is also sponsored by the National Program for Special Supports of Eminent Professionals and the National Program for Support of Top-Notch Young Professionals.

语种：英文

中文关键词：cycle;macrocyclic;conclusion

摘要：Summary of main observation and conclusion Macrocycle has attracted the attention of many researchers in the field of medicinal chemistry due to its unique advantages and good prospects,but the difficulties in drug design and synthesis of macrocycle limit its applications.In this study,a series of macrocyclic derivatives designed from anaplastic lymphoma kinase(ALK)inhibitor lorlatinib were synthesized as Janus kinase 2(JAK2)selective inhibitors.Among them,17f had the best inhibitory activity(IC50=0.177μmol·L^-1)and selectivity for JAK2 over JAK1 and JAK3,which indicated that design of the macrocyclic derivatives might be a feasible strategy for the discovery of novel selective JAK2 inhihitors.