2-(4-chloro-phenyl)-1-methyl-1H-perimidine | 63656-59-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类 - 二氮杂萘
• 英文名称: 2-(4-chloro-phenyl)-1-methyl-1H-perimidine
• 英文别名: Perimidine, 2-(p-chlorophenyl)-1-methyl-；2-(4-chlorophenyl)-1-methylperimidine
• CAS: 63656-59-7
• 化学式: C₁₈H₁₃ClN₂
• 分子量: 292.768
• InChiKey: QSZLTDBMTZWHJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  15.6
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(4-chloro-phenyl)-1-methyl-1H-perimidine 在 溶剂黄146 、 sodium nitrite 、 palladium on activated charcoal 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 生成 、
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel perimidine o-quinone derivatives as non-intercalative topoisomerase II catalytic inhibitors

  摘要：

  For the development of novel anticancer agents, we designed and synthesized a total of 37 perimidine o-quinone derivatives containing the o-quinone group at the A or B ring and different substituents (alkyl groups, aryl groups or heterocycles) at the C ring of the compounds. The structure-activity relationships (SARs) were established based on the cytotoxicity data of compounds from the HL-60, Huh7, Hct116, and Hela cell lines. The cytotoxicity results showed that most compounds exhibited potent cytotoxicity. In particular, compound b-12 showed the best anti-proliferative activity (IC50 <= 1 mu M) against four cancer cell lines and strong potency against the HL-60/MX2 (0.47 mu M) cell line, which is resistant to Topo II poisons. Further studies showed that b-12 exhibited potent Topo II alpha inhibitory activity (IC50 = 7.54 mu M) compared with Topo I, which acted as a class of non-intercalative Topo IIa catalytic inhibitor by inhibiting the ATP binding site of Topo II. Cell apoptosis and cell cycle assays confirmed that b-12 could induce the apoptosis of Huh7 cells in a dose-dependent manner.

  DOI：

  10.1016/j.bioorg.2019.103131
• 作为产物：
  描述：

  4-氯苯甲醛 在 sodium metabisulfite 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 2-(4-chloro-phenyl)-1-methyl-1H-perimidine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel perimidine o-quinone derivatives as non-intercalative topoisomerase II catalytic inhibitors

  摘要：

  For the development of novel anticancer agents, we designed and synthesized a total of 37 perimidine o-quinone derivatives containing the o-quinone group at the A or B ring and different substituents (alkyl groups, aryl groups or heterocycles) at the C ring of the compounds. The structure-activity relationships (SARs) were established based on the cytotoxicity data of compounds from the HL-60, Huh7, Hct116, and Hela cell lines. The cytotoxicity results showed that most compounds exhibited potent cytotoxicity. In particular, compound b-12 showed the best anti-proliferative activity (IC50 <= 1 mu M) against four cancer cell lines and strong potency against the HL-60/MX2 (0.47 mu M) cell line, which is resistant to Topo II poisons. Further studies showed that b-12 exhibited potent Topo II alpha inhibitory activity (IC50 = 7.54 mu M) compared with Topo I, which acted as a class of non-intercalative Topo IIa catalytic inhibitor by inhibiting the ATP binding site of Topo II. Cell apoptosis and cell cycle assays confirmed that b-12 could induce the apoptosis of Huh7 cells in a dose-dependent manner.

  DOI：

  10.1016/j.bioorg.2019.103131

文献信息

• POZHARSKIJ A. F.; KOMISSAROV I. V.; FILIPPOV I. T.; KONSTANTINCHENKO A. A+, XIM.-FARMATSEVT. ZH., 1977, 11, HO 5, 87-93
  作者：POZHARSKIJ A. F.、 KOMISSAROV I. V.、 FILIPPOV I. T.、 KONSTANTINCHENKO A. A+

  DOI：——

  日期：——
• Design, synthesis and biological evaluation of novel perimidine o-quinone derivatives as non-intercalative topoisomerase II catalytic inhibitors
  作者：Du-Chao Zhou、Yu-Ting Lu、Yan-Wen Mai、Chen Zhang、Jie Xia、Pei-Fen Yao、Hong-Gen Wang、Shi-Liang Huang、Zhi-Shu Huang

  DOI：10.1016/j.bioorg.2019.103131

  日期：2019.10

  For the development of novel anticancer agents, we designed and synthesized a total of 37 perimidine o-quinone derivatives containing the o-quinone group at the A or B ring and different substituents (alkyl groups, aryl groups or heterocycles) at the C ring of the compounds. The structure-activity relationships (SARs) were established based on the cytotoxicity data of compounds from the HL-60, Huh7, Hct116, and Hela cell lines. The cytotoxicity results showed that most compounds exhibited potent cytotoxicity. In particular, compound b-12 showed the best anti-proliferative activity (IC50 <= 1 mu M) against four cancer cell lines and strong potency against the HL-60/MX2 (0.47 mu M) cell line, which is resistant to Topo II poisons. Further studies showed that b-12 exhibited potent Topo II alpha inhibitory activity (IC50 = 7.54 mu M) compared with Topo I, which acted as a class of non-intercalative Topo IIa catalytic inhibitor by inhibiting the ATP binding site of Topo II. Cell apoptosis and cell cycle assays confirmed that b-12 could induce the apoptosis of Huh7 cells in a dose-dependent manner.