(E)-[2-hydroxy-4-((2-((benzo[d][1,3]dioxolan-5-yl)methyl)thiazol-4-yl)methoxy)benzaldehyde]-N⁴-[6-(4-methylpiperidin-1-yl)methylbenzo[d]thiazol-2-yl]semicarbazone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: (E)-[2-hydroxy-4-((2-((benzo[d][1,3]dioxolan-5-yl)methyl)thiazol-4-yl)methoxy)benzaldehyde]-N⁴-[6-(4-methylpiperidin-1-yl)methylbenzo[d]thiazol-2-yl]semicarbazone
• 英文别名: (E)-N-(6-((4-methylpiperidin-1-yl)methyl)benzo[d]thiazol-2-yl)-2-(4-((2-(benzo[d][1,3]-dioxol-5-ylmethyl)thiazol-4-yl)methoxy)-2-hydroxybenzylidene)hydrazinecarboxamide；1-[(E)-[4-[[2-(1,3-benzodioxol-5-ylmethyl)-1,3-thiazol-4-yl]methoxy]-2-hydroxyphenyl]methylideneamino]-3-[6-[(4-methylpiperidin-1-yl)methyl]-1,3-benzothiazol-2-yl]urea
• 化学式: C₃₄H₃₄N₆O₅S₂
• 分子量: 670.813
• InChiKey: AKOGMXLERGXLPZ-QNVXDBMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  187
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1,3-苯并二氧杂环戊烯-5-乙腈 在 sodium hydrogen sulfide 、 magnesium(II) chloride hexahydrate 、 碳酸氢钠 、 溶剂黄146 、 potassium iodide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 27.0h， 生成 (E)-[2-hydroxy-4-((2-((benzo[d][1,3]dioxolan-5-yl)methyl)thiazol-4-yl)methoxy)benzaldehyde]-N⁴-[6-(4-methylpiperidin-1-yl)methylbenzo[d]thiazol-2-yl]semicarbazone
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents

  摘要：

  A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to excellent activity against all the tested cell lines. Among them, compounds 15g (procaspase-3 EC50 = 1.42 mu M) and 16b (procaspase-3 EC50 = 0.25 mu M) exhibited excellent antitumor activity with IC50 values ranging from 0.14 mu M to 0.98 mu M against all cancer cell lines, which were 1.8-8.7 times more active than the first procaspase activating compound (PAC-1) (procaspase-3 EC50 = 4.08 mu M). The structure activity relationship (SAR) analyses indicated that the introduction of a lipophilic group (a benzyloxy or heteroaryloxy group) at the 4-position of the 2-hydroxy phenyl ring was beneficial to antitumor activity, and the presence of substituents containing nitrogen that are positively charged at physiological pH could also improve antitumor activity. It was also confirmed that the steric effect of the 4-position substituent of the benzyloxy group had a significant influence on cytotoxic activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.08.058

文献信息

• Design, synthesis, and structure–activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents
  作者：Junjie Ma、Dong Chen、Kuan Lu、Lihui Wang、Xiaoqi Han、Yanfang Zhao、Ping Gong

  DOI：10.1016/j.ejmech.2014.08.058

  日期：2014.10

  A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to excellent activity against all the tested cell lines. Among them, compounds 15g (procaspase-3 EC50 = 1.42 mu M) and 16b (procaspase-3 EC50 = 0.25 mu M) exhibited excellent antitumor activity with IC50 values ranging from 0.14 mu M to 0.98 mu M against all cancer cell lines, which were 1.8-8.7 times more active than the first procaspase activating compound (PAC-1) (procaspase-3 EC50 = 4.08 mu M). The structure activity relationship (SAR) analyses indicated that the introduction of a lipophilic group (a benzyloxy or heteroaryloxy group) at the 4-position of the 2-hydroxy phenyl ring was beneficial to antitumor activity, and the presence of substituents containing nitrogen that are positively charged at physiological pH could also improve antitumor activity. It was also confirmed that the steric effect of the 4-position substituent of the benzyloxy group had a significant influence on cytotoxic activity. (C) 2014 Elsevier Masson SAS. All rights reserved.