Design, Synthesis and Structure-Activity Relationship Study of Pyri-midine-Fused Diazepine Derivatives as L3MBTL3 Inhibitors

doi:10.6023/cjoc201607001

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (12): 2948-2959.DOI: 10.6023/cjoc201607001 Previous Articles Next Articles

ARTICLE

嘧啶并二氮(艹卓)类化合物作为L3MBTL3抑制剂的设计、合成与构效关系研究

周皓, 车鑫, 鲍国臣, 王娜, 柏旭

吉林大学药学院吉林大学组合化学与创新药物研究中心长春 130021

收稿日期:2016-07-01 修回日期:2016-08-03 发布日期:2016-08-12
通讯作者: 柏旭 E-mail:xbai@jlu.edu.cn
基金资助:
国家自然科学基金（No. 81072526）和吉林省科技发展计划重点（No. 20140309010YY）资助项目.

Design, Synthesis and Structure-Activity Relationship Study of Pyri-midine-Fused Diazepine Derivatives as L3MBTL3 Inhibitors

Zhou Hao, Che Xin, Bao Guochen, Wang Na, Bai Xu

Center for Combinatorial Chemistry and Drug Discovery of Jilin University, School of Pharmaceutical Sciences, Changchun 130021

Received:2016-07-01 Revised:2016-08-03 Published:2016-08-12
Supported by:
Project supported by the National Natural Science Foundation of China (No. 81072526) and the Science and Technology Development Plan of Jilin Province (No. 20140309010YY).

Histone methylation is one of epigenetic marks and its deregulation is linked to many diseases. Malignant brain tumor (MBT) domain protein is one of proteins that could read methylated lysine (Kme) of histones. L3MBTL1, a representative member of the MBT family, is related to transcriptional repression, hematopoietic function and tumor formation. Developing a potent and selective inhibitor of L3MBTL1 can help explain the regulatory mechanisms and validate its drugability. Active compound 1 for L3MBTL3 from a library of pyrimidine-fused diazepines was initially obtained. By incorporating the structural features of reported binders, the structure-activity relationship (SAR) studies were conducted, which led to four novel L3MBTL3 inhibitors with IC₅₀ values under 1 μmol·L^-1.

Key words: pyrimidine-fused diazepine, L3MBTL3, inhibitor, SAR study

Cite this article

Zhou Hao, Che Xin, Bao Guochen, Wang Na, Bai Xu. Design, Synthesis and Structure-Activity Relationship Study of Pyri-midine-Fused Diazepine Derivatives as L3MBTL3 Inhibitors[J]. Chin. J. Org. Chem., 2016, 36(12): 2948-2959.

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嘧啶并二氮(艹卓)类化合物作为L3MBTL3抑制剂的设计、合成与构效关系研究

Design, Synthesis and Structure-Activity Relationship Study of Pyri-midine-Fused Diazepine Derivatives as L3MBTL3 Inhibitors

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