Design, synthesis and structure-activity relationship study of pyrimidine-fused diazepine derivatives as L3MBTL3 inhibitors

Zhou, H; Che, X; Bao, G; Wang, N; Bai, X

Design, synthesis and structure-activity relationship study of pyrimidine-fused diazepine derivatives as L3MBTL3 inhibitors

Zhou, H Che, X Bao, G

Wang, N Bai, X

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Publisher:: SCIENCE PRESS
Publication Type:: Journal Article
Citation:: Chinese Journal of Organic Chemistry, 2016, 36, (12), pp. 2948-2959
Issue Date:: 2016-12-01

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Field	Value	Language
dc.contributor.author	Zhou, H
dc.contributor.author	Che, X
dc.contributor.author	Bao, G https://orcid.org/0000-0001-5103-5009
dc.contributor.author	Wang, N
dc.contributor.author	Bai, X
dc.date.accessioned	2022-08-15T19:34:40Z
dc.date.available	2022-08-15T19:34:40Z
dc.date.issued	2016-12-01
dc.identifier.citation	Chinese Journal of Organic Chemistry, 2016, 36, (12), pp. 2948-2959
dc.identifier.issn	0253-2786
dc.identifier.uri	http://hdl.handle.net/10453/160234
dc.description.abstract	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.
dc.language	Chinese
dc.publisher	SCIENCE PRESS
dc.relation.ispartof	Chinese Journal of Organic Chemistry
dc.relation.isbasedon	10.6023/cjoc201607001
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Organic Chemistry
dc.title	Design, synthesis and structure-activity relationship study of pyrimidine-fused diazepine derivatives as L3MBTL3 inhibitors
dc.type	Journal Article
utslib.citation.volume	36
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	closed_access	*
dc.date.updated	2022-08-15T19:34:39Z
pubs.issue	12
pubs.publication-status	Published
pubs.volume	36
utslib.citation.issue	12

Abstract:

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.

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http://hdl.handle.net/10453/160234