bis(2-chloroethyl)-[2-(4-amino-phenoxy)ethyl]amine | 774234-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: bis(2-chloroethyl)-[2-(4-amino-phenoxy)ethyl]amine
• 英文别名: 4-[2-[Bis(2-chloroethyl)amino]ethoxy]aniline；4-[2-[bis(2-chloroethyl)amino]ethoxy]aniline
• CAS: 774234-10-5
• 化学式: C₁₂H₁₈Cl₂N₂O
• 分子量: 277.194
• InChiKey: LLGWMPOVOQNRSS-UHFFFAOYSA-N

物化性质

• 沸点：
  356.7±32.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-氯吖啶 、 bis(2-chloroethyl)-[2-(4-amino-phenoxy)ethyl]amine 在 盐酸 作用下， 以 乙醇 、 氯仿 为溶剂， 生成 acridin-9-yl-(4-{2-[bis(2-chloroethyl)amino]ethoxy}phenyl)amine
  参考文献：
  名称：

  Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation

  摘要：

  A series of 9-anilinoacridine N-mustard derivatives, in which the alkylating N-mustard residue was linked to the C-3' or C-4' position of the anilino ring with an O-ethylene spacer, was synthesized and evaluated for cytotoxicity against human lymphoblastic leukemic cells (CCRF-CEM) in culture. The results showed that all of the new compounds exhibited potent cytotoxicity with IC50 values ranging from 0.002 to 0.7 muM, which were as potent or significantly more potent than 3-(9-acridinylamino)-5-hydroxy-methylaniline (AHMA). Compound 9 did not exhibit cross-resistance against both vinblastine-resistant (CCRF-CEM/VBL) and taxol-resistant (CCRF-CEM/taxol) cells. Additionally, compound 9 demonstrated potent antitumor effect in nude mice bearing human breast carcinoma MX-1 xenografts, resulting in complete tumor remission in two out of three mice at the maximal dose of 1-2 mg/kg (Q3Dx7) or 3 mg/kg (Q4Dx5) via intravenous injection. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.080
• 作为产物：
  描述：

  三(2-氯乙基)胺盐酸盐 在 盐酸 、 potassium fluoride 、 potassium carbonate 、 tin(ll) chloride 作用下， 以 丙酮 为溶剂， 生成 bis(2-chloroethyl)-[2-(4-amino-phenoxy)ethyl]amine
  参考文献：
  名称：

  Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation

  摘要：

  A series of 9-anilinoacridine N-mustard derivatives, in which the alkylating N-mustard residue was linked to the C-3' or C-4' position of the anilino ring with an O-ethylene spacer, was synthesized and evaluated for cytotoxicity against human lymphoblastic leukemic cells (CCRF-CEM) in culture. The results showed that all of the new compounds exhibited potent cytotoxicity with IC50 values ranging from 0.002 to 0.7 muM, which were as potent or significantly more potent than 3-(9-acridinylamino)-5-hydroxy-methylaniline (AHMA). Compound 9 did not exhibit cross-resistance against both vinblastine-resistant (CCRF-CEM/VBL) and taxol-resistant (CCRF-CEM/taxol) cells. Additionally, compound 9 demonstrated potent antitumor effect in nude mice bearing human breast carcinoma MX-1 xenografts, resulting in complete tumor remission in two out of three mice at the maximal dose of 1-2 mg/kg (Q3Dx7) or 3 mg/kg (Q4Dx5) via intravenous injection. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.080

文献信息

• Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity
  作者：Valeriy A. Bacherikov、Ting-Chao Chou、Hua-Jin Dong、Xiuguo Zhang、Ching-Huang Chen、Yi-Wen Lin、Tsong-Jen Tsai、Rong-Zau Lee、Leroy F. Liu、Tsann-Long Su

  DOI：10.1016/j.bmc.2005.03.057

  日期：2005.6

  A series of N-mustard derivatives of 9-anilinoacridine was synthesized for antitumor and structure-activity relationship studies. The alkylating N-mustard residue was linked to the C-3' or C-4' position of the anilino ring with an O-ethylene (O-C-2) O-butylene (O-C-4), and methylene (C-1) spacer. All of the new N-mustard derivatives exhibited significant cytotoxicity in inhibiting human lymphoblastic leukemic cells (CCRF-CEM) in culture. Of these agents, (3-(acridin-9-ylamino)-5-2-[bis(2-chloroethyl)amino]ethoxy}phenyl)methanol (10) was subjected to antitumor studies, resulting in an approximately 100-fold more potent effect than its parent analogue 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) in inhibiting the growth of human lymphoblastic leukemic cells (CCRF-CEM) in vitro. This agent did not exhibit cross-resistance against vinblastine-resistant (CCRF-CEM/VBL) or Taxol-resistant (CCRF-CEM/Taxol) cells. Remarkably, the therapeutic effect of 10 at a dose as low as one tenth of the Taxol therapeutic dose [i.e., 1-2 mg/kg (Q3D x 7) or 3 mg/kg (Q4D x 5); intravenous injection] on nude mice bearing human breast carcinoma MX-1 xenografts resulted in complete tumor remission in two out of three mice. Furthermore, 10 yielded xenograft tumor suppression of 81-96% using human T-cell acute lymphoblastic leukemia CCRF-CEM, colon carcinoma HCT-116, and ovarian adenocarcinoma SK-OV-3 tumor models. (c) 2005 Elsevier Ltd. All rights reserved.
• 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.