2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl(1-((5-amino-4,6-dichloropyrimidin-2-yl)amino) N-2,2,2-trichloroethyl)carbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl(1-((5-amino-4,6-dichloropyrimidin-2-yl)amino) N-2,2,2-trichloroethyl)carbamate
• 英文别名: 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl (2,2,2-trichloro-1-((5-amino-4,6-dichloropyrimidine-2-yl)amino)ethyl)carbamate；2-(2-methyl-5-nitroimidazol-1-yl)ethyl N-[1-[(5-amino-4,6-dichloropyrimidin-2-yl)amino]-2,2,2-trichloroethyl]carbamate
• 化学式: C₁₃H₁₃Cl₅N₈O₄
• 分子量: 522.562
• InChiKey: WBDLMGBMQDZFDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  166
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  甲硝唑 在 ammonium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 21.0h， 生成 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl(1-((5-amino-4,6-dichloropyrimidin-2-yl)amino) N-2,2,2-trichloroethyl)carbamate
  参考文献：
  名称：

  Discovery of a Dual Tubulin Polymerization and Cell Division Cycle 20 Homologue Inhibitor via Structural Modification on Apcin

  摘要：

  Apcin is one of the few compounds that have been previously reported as a Cdc20 specific inhibitor, although Cdc20 is a very promising drug target. We reported here the design, synthesis, and biological evaluations of 2,2,2-trichloro-1-aryl carbamate derivatives as Cdc20 inhibitors. Among these derivatives, compound 9f was much more efficient than the positive compound apcin in inhibiting cancer cell growth, but it had approximately the same binding affinity with apcin in SPR assays. It is possible that another mechanism of action might exist. Further evidence demonstrated that compound 9f also inhibited tubulin polymerization, disorganized the microtubule network, and blocked the cell cycle at the M phase with changes in the expression of cyclins. Thus, it induced apoptosis through the activation of caspase-3 and PARP. In addition, compound 9f inhibited cell migration and invasion in a concentration-dependent manner. These results provide guidance for developing the current series as potential new anticancer therapeutics.

  DOI：

  10.1021/acs.jmedchem.9b02097

文献信息

• Discovery of a Dual Tubulin Polymerization and Cell Division Cycle 20 Homologue Inhibitor via Structural Modification on Apcin
  作者：Pan Huang、Xiangyang Le、Fei Huang、Jie Yang、Haofeng Yang、Junlong Ma、Gaoyun Hu、Qianbin Li、Zhuo Chen

  DOI：10.1021/acs.jmedchem.9b02097

  日期：2020.5.14

  Apcin is one of the few compounds that have been previously reported as a Cdc20 specific inhibitor, although Cdc20 is a very promising drug target. We reported here the design, synthesis, and biological evaluations of 2,2,2-trichloro-1-aryl carbamate derivatives as Cdc20 inhibitors. Among these derivatives, compound 9f was much more efficient than the positive compound apcin in inhibiting cancer cell growth, but it had approximately the same binding affinity with apcin in SPR assays. It is possible that another mechanism of action might exist. Further evidence demonstrated that compound 9f also inhibited tubulin polymerization, disorganized the microtubule network, and blocked the cell cycle at the M phase with changes in the expression of cyclins. Thus, it induced apoptosis through the activation of caspase-3 and PARP. In addition, compound 9f inhibited cell migration and invasion in a concentration-dependent manner. These results provide guidance for developing the current series as potential new anticancer therapeutics.