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Design and Synthesis of a Series of Novel Macrocycle Janus Kinase 2 Inhibitors
Author(s) -
Wang Yanling,
Ge Huan,
Wang Disha,
He Huan,
Li Lu,
Diao Yanyan,
Shen Zihao,
Zhu Lili,
Li Shiliang,
Zhao Zhenjiang,
Li Honglin
Publication year - 2019
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201900316
Subject(s) - chemistry , janus kinase , janus kinase 2 , combinatorial chemistry , anaplastic lymphoma kinase , selectivity , janus , janus kinase 3 , kinase , stereochemistry , nanotechnology , biochemistry , in vitro , medicine , materials science , catalysis , surgery , cytotoxic t cell , antigen presenting cell , pleural effusion , malignant pleural effusion
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 (IC 50 = 0.177 μmol·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 inhibitors.