574738-68-4Relevant articles and documents
Synthesis and antitumor activity evaluation of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at C4-position
Zhang, Ying,Yang, Chao-Rui,Tang, Xue,Cao, Sheng-Li,Ren, Ting-Ting,Gao, Man,Liao, Ji,Xu, Xingzhi
supporting information, p. 4666 - 4670 (2016/09/13)
A series of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at the C4-position were synthesized using piperidine and 1-bromo-3-chloropropane as starting materials via eight steps. Final compounds 8a–q and 9a–i were evaluated for their antiproliferative activity against human lung cancer A549, breast adenocarcinoma MCF-7, and colorectal cancer HCT-116 cell lines. The results showed that fourteen of twenty-six final compounds inhibited the proliferation of three cancer cell lines with IC50values less than 10?μM. When treated with a representative compound 8n, HCT-116 cells were arrested at G0/G1 phase of the cell cycle. This provided a clue to further investigation of the mechanism of action.
Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy- quinazolines
Liu, Feng,Barsyte-Lovejoy, Dalia,Allali-Hassani, Abdellah,He, Yunlong,Herold, J. Martin,Chen, Xin,Yates, Christopher M.,Frye, Stephen V.,Brown, Peter J.,Huang, Jing,Vedadi, Masoud,Arrowsmith, Cheryl H.,Jin, Jian
experimental part, p. 6139 - 6150 (2011/10/09)
Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.
