Identification of novel and improved antimitotic agents derived from noscapine

被引:58
作者
Anderson, JT [1 ]
Ting, AE [1 ]
Boozer, S [1 ]
Brunden, KR [1 ]
Crumrine, C [1 ]
Danzig, J [1 ]
Dent, T [1 ]
Faga, L [1 ]
Harrington, JJ [1 ]
Hodnick, WF [1 ]
Murphy, SM [1 ]
Pawlowski, G [1 ]
Perry, R [1 ]
Raber, A [1 ]
Rundlett, SE [1 ]
Stricker-Krongrad, A [1 ]
Wang, JM [1 ]
Bennani, YL [1 ]
机构
[1] Athersys Inc, Cleveland, OH 44115 USA
关键词
D O I
10.1021/jm050674q
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective 0-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 mu M and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.
引用
收藏
页码:7096 / 7098
页数:3
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