1403583-41-4Relevant 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)
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.
