Design and Synthesis of a Series of Novel Macrocycle Janus Kinase 2 Inhibitors

• 作 者: Yanling Wang Huan Ge Disha Wang Huan He Lu Li Yanyan Diao Zihao Shen Lili Zhu Shiliang Li Zhenjiang Zhao Honglin Li
• 机 构: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and
• 出 处: 中国化学（英文版）
• 发表日期: 2019年12期

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 =0.177 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 inhihitors.