1494589-76-2Relevant academic research and scientific papers
N-ARYL UNSATURATED FUSED RING TERTIARY AMINE COMPOUND, PREPARATION METHOD THEREOF AND ANTITUMOR APPLICATION THEREOF
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Paragraph 0107-0108, (2015/04/15)
The present invention relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, its preparation method, a pharmaceutical composition comprising the compound, and its use in manufacture of a medicament for treatment of a disease or disorder, wherein R1, R2, R5, R6, X, Y, Q, W, n1 and n2 are defined as those stated in the description.
N-Aryl Unsaturated Fused Ring Tertiary Amine Compounds, Preparation Method and Anti-Tumor Applications Thereof
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Paragraph 0182, (2015/05/26)
The present invention relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, its preparation method, a pharmaceutical composition comprising the compound, and its use in manufacture of a medicament for treatment of a disease or disorder, wherein R1, R2, R5, R6, X, Y, Q, W, n1 and n2 are defined as those stated in the description.
Optimization of 4-(N-cycloamino)phenylquinazolines as a novel class of tubulin-polymerization inhibitors targeting the colchicine site
Wang, Xiao-Feng,Guan, Fang,Ohkoshi, Emika,Guo, Wanjun,Wang, Lili,Zhu, Dong-Qing,Wang, Sheng-Biao,Wang, Li-Ting,Hamel, Ernest,Yang, Dexuan,Li, Linna,Qian, Keduo,Morris-Natschke, Susan L.,Yuan, Shoujun,Lee, Kuo-Hsiung,Xie, Lan
, p. 1390 - 1402 (2014/03/21)
The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (1a and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a-c and 5a-m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one (5f), the most potent compound, exhibited high in vitro cytotoxic activity (GI 50 1.9-3.2 nM), significant potency against tubulin assembly (IC 50 0.77 μM), and substantial inhibition of colchicine binding (99% at 5 μM). In mechanism studies, 5f caused cell arrest in G2/M phase, disrupted microtubule formation, and competed mostly at the colchicine site on tubulin. Compound 5f and N-methylated analogue 5g were evaluated in nude mouse MCF7 xenograft models to validate their antitumor activity. Compound 5g displayed significant in vivo activity (tumor inhibitory rate 51%) at a dose of 4 mg/kg without obvious toxicity, whereas 5f unexpectedly resulted in toxicity and death at the same dose.
