N-{4-[bis(2-chloroethyl)amino]phenyl}-2-(6-(2-fluorophenyl)[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinecarboxamide | 1225205-86-6

• 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: N-{4-[bis(2-chloroethyl)amino]phenyl}-2-(6-(2-fluorophenyl)[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinecarboxamide
• CAS: 1225205-86-6
• 化学式: C₂₇H₂₄Cl₂FN₅O₃
• 分子量: 556.424
• InChiKey: FYTBPVABFYHFHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  87.75
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  6-(2-fluorophenyl)-8-hydrazinyl-[1,3]dioxolo[4,5-g]quinoline hydrochloride 、 p-isocyanophenyl mustard 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到N-{4-[bis(2-chloroethyl)amino]phenyl}-2-(6-(2-fluorophenyl)[1,3]dioxolo[4,5-g]quinolin-8-yl)hydrazinecarboxamide
  参考文献：
  名称：

  Potent DNA-directed alkylating agents: Synthesis and biological activity of phenyl N-mustard–quinoline conjugates having a urea or hydrazinecarboxamide linker

  摘要：

  A series of N-mustard-quinoline conjugates bearing a urea or hydrazinecarboxamide linker was synthesized for antitumor evaluation. The in vitro cytotoxicity studies revealed that compounds with hydrazinecarboxamide linkers were generally more cytotoxic than the corresponding urea counterparts in inhibiting human lymphoblastic leukemia and various solid tumor cell growths in culture. The therapeutic efficacy against human tumor xenografts in animal model was studied. It was shown that complete tumor remission in nude mice bearing human breast carcinoma MX-1 xenograft by 17a, i and 18c, d was achieved. In the present study, it was revealed that both linkers are able to lower the chemically reactive N-mustard pharmacophore and thus the newly synthesized conjugates possess a long half-life in rat plasma. Moreover, the new N-mustard derivatives are able to induce DNA cross-linking either by modified comet assay or by alkaline agarose gel shift assay. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.061