574738-68-4Relevant academic research and scientific papers
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
, 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.
Inhibition of tumor cell growth and angiogenesis by 7-Aminoalkoxy-4- aryloxy-quinazoline ureas, a novel series of multi-tyrosine kinase inhibitors
Ravez, Séverine,Barczyk, Amélie,Six, Perrine,Cagnon, Aurélie,Garofalo, Antonio,Goossens, Laurence,Depreux, Patrick
, p. 369 - 381 (2014/05/06)
Several regulatory and signaling molecules governing angiogenesis are targets of interest for the development of drugs in the cancer, including growth factors such as Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF). A series of 4-aryloxy-6,7-dimethoxyquinazolines, previously synthesized in our laboratory, has shown a nanomolar inhibition of kinase enzymatic activity of VEGFR, PDGFR and c-Kit. We have therefore studied the impact of the variation in the 7-position substitution of the quinazoline core. Substitution by aminoalkoxy chains led to new highly potent ATP-competitive inhibitors of VEGFR, PDGFR and c-Kit enzyme with IC50 values in the nanomolar range and this substitution has increased greatly antiproliferative activity on cancer cell lines (PC3, MCF7, HT29) and HUVEC (human umbilical vein endothelial cells). One of the most promising compounds (36) was assessed for its ability to limit the induction of web like network of capillary tubes by the human umbilical vascular endothelial cells (HUVEC) and for its ability to inhibit invasion.
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
, 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.
Improved synthesis of substituted 6,7-dihydroxy-4-quinazolineamines: Tandutinib, erlotinib and gefitinib
Knesl, Petr,Roeseling, Dirk,Jordis, Ulrich
, p. 286 - 297 (2007/10/03)
The synthesis of three substituted 6,7-dihydroxy-4-quinazolineamines: tandutinib (1), erlotinib (2) and gefitinib (3) in improved yields is reported. The intermediates were characterized by NMR and the purities determined by HPLC.
