Chinese Journal of Organic Chemistry >
Design, Synthesis and Structure-Activity Relationship Study of Pyri-midine-Fused Diazepine Derivatives as L3MBTL3 Inhibitors
Received date: 2016-07-01
Revised date: 2016-08-03
Online 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
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]. Chinese Journal of Organic Chemistry, 2016 , 36(12) : 2948 -2959 . DOI: 10.6023/cjoc201607001
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