tert-butyl 4-(((1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)-methylthio)carbonothioyl)piperazine-1-carboxylate | 1418150-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(((1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)-methylthio)carbonothioyl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-(((1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)methylthio)carbonothioyl)piperazine-1-arboxylate；Tert-butyl 4-[[1-[(4-methylphenyl)methyl]triazol-4-yl]methylsulfanylcarbothioyl]piperazine-1-carboxylate；tert-butyl 4-[[1-[(4-methylphenyl)methyl]triazol-4-yl]methylsulfanylcarbothioyl]piperazine-1-carboxylate
• CAS: 1418150-16-9
• 化学式: C₂₁H₂₉N₅O₂S₂
• 分子量: 447.626
• InChiKey: IVYXCBVBLKBRMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(((1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)-methylthio)carbonothioyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)methyl piperazine-1-carbodithioate
  参考文献：
  名称：

  Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents

  摘要：

  A series of novel 1,2,3-triazole-dithiocarbamate hybrids were designed, synthesized and evaluated for anticancer activity against four selected human tumor cell lines (MGC-803, MCF-7, PC-3, EC-109). Majority of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 3a and 3c showed excellent broad spectrum anticancer activity with IC50 values ranging from 0.73 to 11.61 mu M and 0.49-12.45 mu M, respectively. Particularly, compound 3a was more potent than 5-fluorouracil against all tested human cancer cell lines. Flow cytometry analysis demonstrated that treatment of MGC-803 with 3c led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death after 12 h. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.12.046
• 作为产物：
  描述：

  N-Boc-哌嗪 在 sodium phosphate dodecahydrate 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 3.0h， 生成 tert-butyl 4-(((1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)-methylthio)carbonothioyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Triazole–Dithiocarbamate Based Selective Lysine Specific Demethylase 1 (LSD1) Inactivators Inhibit Gastric Cancer Cell Growth, Invasion, and Migration

  摘要：

  Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD l's expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1,2,3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and robust inhibition of LSD1. Interestingly, compound 26 also showed potent and selective cytotoxicity against LSD1 overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore, compound 26 effectively reduced the tumor growth bared by human gastric cancer cells in vivo with no signs of adverse side effects. These findings suggested that compound 26 deserves further investigation as a lead compound in the treatment of LSD1 overexpressing gastric cancer.

  DOI：

  10.1021/jm401002r

文献信息

• Triazole–Dithiocarbamate Based Selective Lysine Specific Demethylase 1 (LSD1) Inactivators Inhibit Gastric Cancer Cell Growth, Invasion, and Migration
  作者：Yi-Chao Zheng、Ying-Chao Duan、Jin-Lian Ma、Rui-Min Xu、Xiaolin Zi、Wen-Lei Lv、Meng-Meng Wang、Xian-Wei Ye、Shun Zhu、David Mobley、Yan-Yan Zhu、Jun-Wei Wang、Jin-Feng Li、Zhi-Ru Wang、Wen Zhao、Hong-Min Liu

  DOI：10.1021/jm401002r

  日期：2013.11.14

  Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD l's expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1,2,3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and robust inhibition of LSD1. Interestingly, compound 26 also showed potent and selective cytotoxicity against LSD1 overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore, compound 26 effectively reduced the tumor growth bared by human gastric cancer cells in vivo with no signs of adverse side effects. These findings suggested that compound 26 deserves further investigation as a lead compound in the treatment of LSD1 overexpressing gastric cancer.
• Design, synthesis and antiproliferative activity studies of novel 1,2,3-triazole–dithiocarbamate–urea hybrids
  作者：Ying-Chao Duan、Yi-Chao Zheng、Xiao-Chen Li、Meng-Meng Wang、Xian-Wei Ye、Yuan-Yuan Guan、Gai-Zhi Liu、Jia-Xin Zheng、Hong-Min Liu

  DOI：10.1016/j.ejmech.2013.03.058

  日期：2013.6

  A series of novel 1,2,3-triazole-dithiocarbamate-urea hybrids were designed, synthesized and their antiproliferative activities against four selected human cancer cell lines were evaluated. The results showed that a number of the hybrids exhibited potent activity in selected human cancer cell lines. Among them, compounds 27 and 34 showed broad spectrum anticancer activity with IC50 values ranging from 1.62 to 20.84 mu M and 0.76 to 13.55 mu M, respectively. Interestingly, compounds 27 and 34, being very potent against MGC-803 cells, exhibited no significant cytotoxicity against normal human embryonic kidney cells at up to 55 mu M and 70 mu M, respectively. Evidences of cell cycle arrest and apoptosis induction were obtained for the most effective compounds 27 and 34 by means of flow cytometry and microscopic techniques. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents
  作者：Ying-Chao Duan、Yong-Cheng Ma、En Zhang、Xiao-Jing Shi、Meng-Meng Wang、Xian-Wei Ye、Hong-Min Liu

  DOI：10.1016/j.ejmech.2012.12.046

  日期：2013.4

  A series of novel 1,2,3-triazole-dithiocarbamate hybrids were designed, synthesized and evaluated for anticancer activity against four selected human tumor cell lines (MGC-803, MCF-7, PC-3, EC-109). Majority of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 3a and 3c showed excellent broad spectrum anticancer activity with IC50 values ranging from 0.73 to 11.61 mu M and 0.49-12.45 mu M, respectively. Particularly, compound 3a was more potent than 5-fluorouracil against all tested human cancer cell lines. Flow cytometry analysis demonstrated that treatment of MGC-803 with 3c led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death after 12 h. (C) 2013 Elsevier Masson SAS. All rights reserved.