4-{4-[bis(2-chloroethyl)-amino]butoxy}-9-chloro acridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-{4-[bis(2-chloroethyl)-amino]butoxy}-9-chloro acridine
• 英文别名: 4-(9-chloroacridin-4-yl)oxy-N,N-bis(2-chloroethyl)butan-1-amine
• 化学式: C₂₁H₂₃Cl₃N₂O
• 分子量: 425.785
• InChiKey: FGXNGPUJLZIFGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-{4-[bis(2-chloroethyl)-amino]butoxy}-9-chloro acridine 、 2,4-二氨基甲苯 在 N-甲基吗啉 作用下， 以 乙醇 为溶剂， 生成 N1-(4-{4-[bis(2-chloroethyl)amino]butoxy}acridin-9-yl)-4-methylbenzene-1,3-diamine
  参考文献：
  名称：

  Potent Antitumor 9-Anilinoacridines and Acridines Bearing an Alkylating N-Mustard Residue on the Acridine Chromophore:  Synthesis and Biological Activity

  摘要：

  A series of 9-anilinoacridine and acridine derivatives bearing an alkylating N-mustard residue at C4 of the acridine chromophore were synthesized. The N-mustard pharmacophore was linked to the C4 of the acridine ring with an O-ethyl ( O-C-2), O-propyl ( O-C-3), or O-butyl ( O-C-4) spacer. It revealed that all newly synthesized compounds were very potent cytotoxic agents against human leukemia and various solid tumors in vitro. These agents did not exhibit cross-resistance against vinblastine-resistant ( CCRF-CEM/VBL) or taxol-resistant ( CCRF-CEM/taxol) cells. It also showed that these agents were DNA cross-linking agents rather than topoisomerase II inhibitors. Of these agents, compounds 27a and 27c were shown to have potent antitumor activity in nude mice bearing the human breast carcinoma MX-1 xenograft. The therapeutic efficacies of these two agents are comparable to that of taxol.

  DOI：

  10.1021/jm060197r
• 作为产物：
  描述：

  4-hydroxy-9-oxoacridine 在 氯化亚砜 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 氯仿 、 二乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 75.17h， 生成 4-{4-[bis(2-chloroethyl)-amino]butoxy}-9-chloro acridine
  参考文献：
  名称：

  Potent Antitumor 9-Anilinoacridines and Acridines Bearing an Alkylating N-Mustard Residue on the Acridine Chromophore:  Synthesis and Biological Activity

  摘要：

  A series of 9-anilinoacridine and acridine derivatives bearing an alkylating N-mustard residue at C4 of the acridine chromophore were synthesized. The N-mustard pharmacophore was linked to the C4 of the acridine ring with an O-ethyl ( O-C-2), O-propyl ( O-C-3), or O-butyl ( O-C-4) spacer. It revealed that all newly synthesized compounds were very potent cytotoxic agents against human leukemia and various solid tumors in vitro. These agents did not exhibit cross-resistance against vinblastine-resistant ( CCRF-CEM/VBL) or taxol-resistant ( CCRF-CEM/taxol) cells. It also showed that these agents were DNA cross-linking agents rather than topoisomerase II inhibitors. Of these agents, compounds 27a and 27c were shown to have potent antitumor activity in nude mice bearing the human breast carcinoma MX-1 xenograft. The therapeutic efficacies of these two agents are comparable to that of taxol.

  DOI：

  10.1021/jm060197r

文献信息

• Synthesis and in vitro cytotoxicity of 9-anilinoacridines bearing N-mustard residue on both anilino and acridine rings
  作者：Ching-Huang Chen、Yi-Wen Lin、Xiuguo Zhang、Ting-Chao Chou、Tsong-Jen Tsai、Naval Kapuriya、Rajesh Kakadiya、Tsann-Long Su

  DOI：10.1016/j.ejmech.2008.07.016

  日期：2009.7

  A series of 9-anilinoacridines having an alkylating N-mustard pharmacophore on both anilino (C-3' or C-4') and acridine (C-4) rings with O-ethyl (O-C-2) or O-butyl (O-C-4) spacer were synthesized to evaluate their cytotoxicity against human lymphoblastic leukemia (CCRF-CEM) cell growth in vitro. It was revealed that these conjugates exhibited significant in vitro cytotoxicity. Among these agents, compound 13 was the most cytotoxic with IC50 value of 1.3 nM and is as potent as taxol (IC50 = 1.1 nM). The structure-activity relationship study showed that the length of the spacer and the position of the substituent do affect their cytotoxicity. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Potent Antitumor 9-Anilinoacridines and Acridines Bearing an Alkylating <i>N</i>-Mustard Residue on the Acridine Chromophore:  Synthesis and Biological Activity
  作者：Tsann-Long Su、Yi-Wen Lin、Ting-Chao Chou、Xiuguo Zhang、Valeriy A. Bacherikov、Ching-Huang Chen、Leroy F. Liu、Tsong-Jen Tsai

  DOI：10.1021/jm060197r

  日期：2006.6.1

  A series of 9-anilinoacridine and acridine derivatives bearing an alkylating N-mustard residue at C4 of the acridine chromophore were synthesized. The N-mustard pharmacophore was linked to the C4 of the acridine ring with an O-ethyl ( O-C-2), O-propyl ( O-C-3), or O-butyl ( O-C-4) spacer. It revealed that all newly synthesized compounds were very potent cytotoxic agents against human leukemia and various solid tumors in vitro. These agents did not exhibit cross-resistance against vinblastine-resistant ( CCRF-CEM/VBL) or taxol-resistant ( CCRF-CEM/taxol) cells. It also showed that these agents were DNA cross-linking agents rather than topoisomerase II inhibitors. Of these agents, compounds 27a and 27c were shown to have potent antitumor activity in nude mice bearing the human breast carcinoma MX-1 xenograft. The therapeutic efficacies of these two agents are comparable to that of taxol.