Synthesis and antitumor activity of novel substituted uracil-1′(N)-acetic acid ester derivatives of 20(S)-camptothecins

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• 作者：Di-Zao Li^a ; ^b ; ¹ ; Qiang-Zhe Zhang^a ; ¹ ; Cun-Ying Wang^c ; ¹ ; Yan-Ling Zhang^d ; ¹ ; Xing-Yu Li^a ; Ji-Tao Huang^a ; Hong-Yan Liu^b ; Zhao-Di Fu^b ; Hua-Xian Song^e ; Jin-Ping Lin^e ; Teng-Fei Ji^b ; ^{jitf@imm.ac.cn} ; Xian-Dao Pan^b ; ^{xdp@imm.ac.cn}
• 关键词：Camptothecin ; Synthesis ; Substituted uracil-1&prime ; (N)-acetic acid ; Antitumor activity ; The mechanism of antitumor activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：1235-1246
• 全文大小：2951 K
• 卷排序：125

文摘

20(S)-uracil-1′(N)-acetic acid CPT-ester derivatives were synthesized. Several analogues exhibited superior cytotoxicity compared to CPT and TPT. 12 possessed higher in vivo antitumor activity and lower toxicity than TPT. The mechanism study revealed that 12 was a Top I inhibitor as same as TPT. 12 is a new class of antitumor clinical trial drug candidate of CPTs.