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

作者：Zhou, Hao; Che, Xin; Bao, Guochen; Wang, Na; Bai, Xu^*

来源：Chinese Journal of Organic Chemistry, 2016, 36(12): 2948-2959.

DOI：10.6023/cjoc201607001

• pyrimidine-fused diazepine
• L3MBTL3
• inhibitor
• SAR study

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 mu mol center dot L-1.

• 出版日期2016-12
• 单位吉林大学