81259-56-5Relevant articles and documents
COMPOUNDS AND USES THEREOF
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Page/Page column 152; 281, (2018/05/17)
The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase
Xiong, Yan,Li, Fengling,Babault, Nicolas,Dong, Aiping,Zeng, Hong,Wu, Hong,Chen, Xin,Arrowsmith, Cheryl H.,Brown, Peter J.,Liu, Jing,Vedadi, Masoud,Jin, Jian
, p. 1876 - 1891 (2017/03/17)
G9a-like protein (GLP) and G9a are highly homologous protein lysine methyltransferases (PKMTs) sharing approximately 80% sequence identity in their catalytic domains. GLP and G9a form a heterodimer complex and catalyze mono- and dimethylation of histone H3 lysine 9 and nonhistone substrates. Although they are closely related, GLP and G9a possess distinct physiological and pathophysiological functions. Thus, GLP or G9a selective small-molecule inhibitors are useful tools to dissect their distinct biological functions. We previously reported potent and selective G9a/GLP dual inhibitors including UNC0638 and UNC0642. Here we report the discovery of potent and selective GLP inhibitors including 4 (MS0124) and 18 (MS012), which are >30-fold and 140-fold selective for GLP over G9a and other methyltransferases, respectively. The cocrystal structures of GLP and G9a in the complex with either 4 or 18 displayed virtually identical binding modes and interactions, highlighting the challenges in structure-based design of selective inhibitors for either enzyme.
Structure-activity relationship studies of SETD8 inhibitors
Ma, Anqi,Yu, Wenyu,Xiong, Yan,Butler, Kyle V.,Brown, Peter J.,Jin, Jian
supporting information, p. 1892 - 1898 (2015/01/08)
SETD8 (also known as SET8, PR-SET7, or KMT5A (lysine methyltransferase 5A)) is the only known lysine methyltransferase that catalyzes the monomethylation of histone H4 lysine 20 (H4K20). In addition to H4K20, SETD8 monomethylates non-histone substrates such as the tumor suppressor p53 and the proliferating cell nuclear antigen (PCNA). Because of its role in regulating diverse biological processes, SETD8 has been pursued as a potential therapeutic target. We recently reported the first substrate-competitive SETD8 inhibitor, UNC0379 (1), which is selective for SETD8 over 15 other methyltransferases. We characterized this inhibitor in a battery of biochemical and biophysical assays. Here we describe our comprehensive structure-activity relationship (SAR) studies of this chemical series. In addition to 2- and 4-substituents, we extensively explored 6- and 7-substituents of the quinazoline scaffold. These SAR studies led to the discovery of several new compounds, which displayed similar potencies as compound 1 and interesting SAR trends. This journal is
Synthesis and biological evaluation of substituted 1,2,3-benzotriazines and pyrido[3,2-d]-1,2,3-triazines as inhibitors of vascular endothelial growth factor receptor-2
Zhao, Xing-Wang,Liu, Dan,Luan, Sheng-Lin,Hu, Guo-Dong,Lv, Jin-Ling,Jing, Yong-Kui,Zhao, Lin-Xiang
, p. 7807 - 7815 (2014/01/06)
A novel series of substituted 1,2,3-benzotriazines and pyrido[3,2-d]-1,2,3- triazines were synthesized. The abilities of these compounds to inhibit the VEGFR-2 kinase activity and the proliferation of human microvascular endothelial cells (MVECs) were det
Design, synthesis, and antitumor activities of some novel substituted 1,2,3-benzotriazines
Lv, Jin-Ling,Wang, Rui,Liu, Dan,Guo, Gang,Jing, Yong-Kui,Zhao, Lin-Xiang
, p. 1427 - 1440 (2008/12/20)
A series of novel substituted 1,2,3-benzotriazines based on the structures of vatalanib succinate (PTK787) and vandetanib (ZD6474) were designed and synthesized. The antiproliferative effects of these compounds were tested on microvascular endothelial cel
An efficient method for the preparation of nitriles via the dehydration of aldoximes with phthalic anhydride
Wang, Eng-Chi,Huang, Keng-Shiang,Chen, Hsing-Ming,Wu, Chung-Chin,Lin, Gwo-Jiun
, p. 619 - 627 (2007/10/03)
A new and highly efficient method for the conversion of aldoximes to nitriles was established. By fusing with phthalic anhydride, aldoximes were efficiently and smoothly converted into nitriles, in high yields (over 85%) and in a short time (within 5 minutes). The mixture of phthalic anhydride, a cyclic anhydride, and aldoximes in fusing state set up an ideal transition state for a selective [3.3]-sigmatropic rearrangement of the acylated aldoximes to nitriles.
Anthranilic acid derivatives as inhibitors of the cGMP-phosphodiesterase
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, (2008/06/13)
Compounds of formula (I) STR1where R 1 is hydrogen; R 2 is nitro, cyano or halo(lower)alkyl; R 3 is phenyl substituted with one or more substituents selected from halogen, cyano and lower alkoxy; A is a lower alkylene group; R 4 is a group CR 6 R 7 R 8 wherein R 6 and R 7 form, together with the carbon atom to which they are attached a cycloalkyl group optionally substituted with hydroxy, lower alkoxy or a lower alkanoylamino; and R 8 is hydrogen; its prodrug and a salt thereof.
