N,N-二(2-氯乙基)-4-甲硫基苯胺 | 64977-17-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: N,N-二(2-氯乙基)-4-甲硫基苯胺
• 英文名称: N,N-bis-(2-chloroethyl)-4-(methylthio)aniline
• 英文别名: N,N-bis(2-chloroethyl)-4-(methylthio)aniline；p-(methylthio)-N,N-bis(2-chloroethyl)aniline；N,N-bis-(2-chloro-ethyl)-4-methylsulfanyl-aniline；N,N-Bis-(2-chlor-aethyl)-4-methylmercapto-anilin；Benzenamine, N,N-bis(2-chloroethyl)-4-(methylthio)-；N,N-bis(2-chloroethyl)-4-methylsulfanylaniline
• CAS: 64977-17-9
• 化学式: C₁₁H₁₅Cl₂NS
• 分子量: 264.219
• InChiKey: GQILSBKHQTYPGZ-UHFFFAOYSA-N

物化性质

• 沸点：
  383.3±37.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  28.5
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  N,N-二(2-氯乙基)-4-甲硫基苯胺 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以82%的产率得到methyl N,N-bis(2-chloroethyl)-4-aminophenyl sulfone
  参考文献：
  名称：

  Hypoxia-selective antitumor agents. 3. Relationships between structure and cytotoxicity against cultured tumor cells for substituted N,N-bis(2-chloroethyl)anilines

  摘要：

  A series of aniline mustards with a wide range of electron-donating and -withdrawing substituents in the 3- and 4-positions has been synthesized and evaluated for cytotoxicity in cell culture to examine the potential of using nitro group deactivated nitrogen mustards for the design of novel hypoxia-selective anticancer drugs (Denny, W. A.; Wilson, W. R. J. Med. Chem. 1986, 29, 879). Hydrolytic half-lives in tissue culture media, determined by bioassay against a cell line (UV4) defective in the repair of DNA interstrand cross-links showed the expected dependence on the Hammett electronic parameter, sigma, varying from 0.13 h for the 4-amino analogue to greater than 100 h for analogues with strongly electron-withdrawing substituents. Cytotoxic potencies in aerobic UV4 cultures showed a similar dependence on sigma. This dependence predicted that the 4-nitroaniline mustard would be 7200-fold less potent than its potential six-electron reduction product, the 4-amino compound, in growth inhibition assays using a 1-h drug exposure. The measured differential was much lower (225-fold) because of the instability of the latter compound, but a differential of 17,500-fold was observed in the initial rate of killing by using a clonogenic assay. The potential for formation of reactive mustards by reduction to the amine or hydroxylamine was demonstrated by the 4-nitroso compound, which had an aerobic toxicity similar to that of the amine. Although these features confirmed the original rationale, the 3-nitro- and 4-nitroaniline mustards had only minimal hypoxic selectivity against UV cells. Toxicity to hypoxic cells appears to be limited by the low reduction potentials of these compounds and consequent lack of enzymatic nitroreduction. However, this study has demonstrated that nitro groups can be used to latentiate aromatic nitrogen mustards and indicates that examples with higher reduction potentials could provide useful hypoxia-selective therapeutic agents.

  DOI：

  10.1021/jm00163a019
• 作为产物：
  描述：

  bis-{4-[bis-(2-hydroxy-ethyl)-amino]-phenyl}-disulfide 在 lithium aluminium tetrahydride 、 三氯氧磷 作用下， 生成 N,N-二(2-氯乙基)-4-甲硫基苯胺
  参考文献：
  名称：

  Benn et al., Journal of the Chemical Society, 1958, p. 2800,2804

  摘要：

  DOI：

文献信息

• F-18 labelledN,N-bis-haloethylamino-phenylsulfoxides — a new class of compounds for the imaging of hypoxic tissue
  作者：Cheryl L. Falzon、Uwe Ackermann、Neil Spratt、Henri J. Tochon-Danguy、Jonathon White、David Howells、Andrew M. Scott

  DOI：10.1002/jlcr.1129

  日期：2006.10.30

  Two N,N-bis-chloroethylamino-phenylsulfoxides have been synthesized and radiolabelled with F-18 via halogen exchange. The radiolabelling of both compounds proceeds smoothly with K[18F]F-kryptofix 2.2.2 complex at 100 °C in DMSO. Decay-corrected radiochemical yields were 25–35% for [18F]12 (SO201) and 35–45% for [18F]11 (SO101), with an average specific activity of 1.8 Ci/µmol. Both compounds remained 80% intact in plasma over a period of 2 h. In vivo binding in a stroke model indicates that both markers are selectively retained in hypoxic tissue. Copyright © 2006 John Wiley & Sons, Ltd.

  我们合成了两种 N,N-双氯乙基氨基苯基硫氧化物，并通过卤素交换用 F-18 进行了放射性标记。在 100 °C 的二甲基亚砜中，这两种化合物与 K[18F]F-kryptofix 2.2.2 复合物一起顺利进行放射性标记。衰变校正放射化学产率为：[18F]12 (SO201) 25-35%，[18F]11 (SO101)35-45%，平均比活度为 1.8 Ci/µmol。在中风模型中的体内结合表明，这两种标记物都能选择性地保留在缺氧组织中。Copyright © 2006 John Wiley & Sons, Ltd. All Rights Reserved.
• Lecocq, Bulletin de la Societe Chimique de France, 1950, p. 188,190
  作者：Lecocq

  DOI：——

  日期：——
• p-(Methylsulfinyl)phenyl nitrogen mustard as a novel bioreductive prodrug selective against hypoxic tumors
  作者：Chul Hoon Kwon、Daria R. Blanco、Nesrine Baturay

  DOI：10.1021/jm00089a027

  日期：1992.5
• Benn et al., Journal of the Chemical Society, 1958, p. 2800,2804
  作者：Benn et al.

  DOI：——

  日期：——
• Hypoxia-selective antitumor agents. 3. Relationships between structure and cytotoxicity against cultured tumor cells for substituted N,N-bis(2-chloroethyl)anilines
  作者：Brian D. Palmer、William R. Wilson、Susan M. Pullen、William A. Denny

  DOI：10.1021/jm00163a019

  日期：1990.1

  A series of aniline mustards with a wide range of electron-donating and -withdrawing substituents in the 3- and 4-positions has been synthesized and evaluated for cytotoxicity in cell culture to examine the potential of using nitro group deactivated nitrogen mustards for the design of novel hypoxia-selective anticancer drugs (Denny, W. A.; Wilson, W. R. J. Med. Chem. 1986, 29, 879). Hydrolytic half-lives in tissue culture media, determined by bioassay against a cell line (UV4) defective in the repair of DNA interstrand cross-links showed the expected dependence on the Hammett electronic parameter, sigma, varying from 0.13 h for the 4-amino analogue to greater than 100 h for analogues with strongly electron-withdrawing substituents. Cytotoxic potencies in aerobic UV4 cultures showed a similar dependence on sigma. This dependence predicted that the 4-nitroaniline mustard would be 7200-fold less potent than its potential six-electron reduction product, the 4-amino compound, in growth inhibition assays using a 1-h drug exposure. The measured differential was much lower (225-fold) because of the instability of the latter compound, but a differential of 17,500-fold was observed in the initial rate of killing by using a clonogenic assay. The potential for formation of reactive mustards by reduction to the amine or hydroxylamine was demonstrated by the 4-nitroso compound, which had an aerobic toxicity similar to that of the amine. Although these features confirmed the original rationale, the 3-nitro- and 4-nitroaniline mustards had only minimal hypoxic selectivity against UV cells. Toxicity to hypoxic cells appears to be limited by the low reduction potentials of these compounds and consequent lack of enzymatic nitroreduction. However, this study has demonstrated that nitro groups can be used to latentiate aromatic nitrogen mustards and indicates that examples with higher reduction potentials could provide useful hypoxia-selective therapeutic agents.