ethyl 3-[4-(N,N-bis(2-chloroethyl)amino)phenyl]propanoate | 64977-23-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ethyl 3-[4-(N,N-bis(2-chloroethyl)amino)phenyl]propanoate
• 英文别名: 3-{4-[bis-(2-chloro-ethyl)-amino]-phenyl}-propionic acid ethyl ester；3-{4-[Bis-(2-chlor-aethyl)-amino]-phenyl}-propionsaeure-aethylester；Ethyl 3-[4-[bis(2-chloroethyl)amino]phenyl]propanoate；ethyl 3-[4-[bis(2-chloroethyl)amino]phenyl]propanoate
• CAS: 64977-23-7
• 化学式: C₁₅H₂₁Cl₂NO₂
• 分子量: 318.243
• InChiKey: HHUOBTYCWFBNAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-[4-(N,N-bis(2-chloroethyl)amino)phenyl]propanoate 在 盐酸 作用下， 反应 4.0h， 以97.8%的产率得到4-[二(2-氯乙基)氨基]氢化肉桂酸
  参考文献：
  名称：

  Coronarin D Conjugated to Methylene Homologues of Chlorambucil: Synthesis and Evaluation of their Cytotoxicity

  摘要：

  合成了氯丁嘧啶的亚甲基同系物，并将其与唇烃二萜冠醚萜 D 共轭。对这些产品进行了体外细胞毒性评估，发现它们对 MOLT-3 细胞系具有选择性活性。氯霉素的两种同系物显示出与其母体相当的细胞毒性作用。不过，与未减活化的氯丁氨嘧啶及其同系物相比，它们通过酯键与冠突散囊菌素 D 共轭并没有增强对受测癌细胞株的体外细胞毒性。

  DOI：

  10.3184/174751912x13362343090928
• 作为产物：
  描述：

  N,N-二羟乙基苯胺 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙酸乙酯 、 1,2-二氯乙烷 、 mineral oil 为溶剂， 反应 6.67h， 生成 ethyl 3-[4-(N,N-bis(2-chloroethyl)amino)phenyl]propanoate
  参考文献：
  名称：

  Coronarin D Conjugated to Methylene Homologues of Chlorambucil: Synthesis and Evaluation of their Cytotoxicity

  摘要：

  合成了氯丁嘧啶的亚甲基同系物，并将其与唇烃二萜冠醚萜 D 共轭。对这些产品进行了体外细胞毒性评估，发现它们对 MOLT-3 细胞系具有选择性活性。氯霉素的两种同系物显示出与其母体相当的细胞毒性作用。不过，与未减活化的氯丁氨嘧啶及其同系物相比，它们通过酯键与冠突散囊菌素 D 共轭并没有增强对受测癌细胞株的体外细胞毒性。

  DOI：

  10.3184/174751912x13362343090928

文献信息

• Design, synthesis and biological evaluation of novel sesquiterpene mustards as potential anticancer agents
  作者：Yuan-Zhen Xu、Xue-Yan Gu、Shou-Jiao Peng、Jian-Guo Fang、Ying-Mei Zhang、De-Jun Huang、Jian-Jun Chen、Kun Gao

  DOI：10.1016/j.ejmech.2015.03.001

  日期：2015.4

  Several novel series of sesquiterpene mustards (SMs) bearing nitrogen mustard and glutathione (GSH)-reactive alpha-methylene-gamma-butyrolactone groups were successfully prepared for the first time and showed excellent antiproliferative activities in vitro. Among them, compounds 2e and 2g displayed the highest antiproliferative properties with IC50 values ranging from 2.5 to 8.7 mu M. The selectivity of these two compounds was evaluated by SRB method against human cancer and normal hepatic cells (HepG2 and L02). The induction of apoptosis and effects on the cell cycle distribution with compounds 2e and 2g were investigated by Hoechst 33,258 staining and flow cytometry, which exhibited that they could induce selective cell apoptosis and cell cycle arrest in HepG2 and L02 cells. In addition, further investigation showed that compounds 2e and 2g could obviously inhibit the proliferation of HepG2 cells by inducing significant DNA cross-linking and depleting GSH in cell media. The good cytotoxicity and selectivity of compounds 2e and 2g pointed them as promising leads for anticancer drug design. (C) 2015 Published by Elsevier Masson SAS.
• Everett et al., Journal of the Chemical Society, 1953, p. 2386,2387
  作者：Everett et al.

  DOI：——

  日期：——
• Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA
  作者：Kun Fang、Guoqiang Dong、Hongyu Wang、Shipeng He、Shanchao Wu、Wei Wang、Chunquan Sheng

  DOI：10.1002/cmdc.201700666

  日期：2018.1.8

  Herein we report the first exploration of a dual‐targeting drug design strategy to improve the efficacy of small‐molecule cancer immunotherapy. New hybrids of indoleamine 2,3‐dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first‐in‐class examples of such molecules, they were found to exhibit significantly enhanced

  在此，我们报告了首次探索双重靶向药物设计策略以提高小分子癌症免疫疗法的功效。合理设计了吲哚胺2，3-二加氧酶1（IDO1）抑制剂和分别将IDO1和DNA分别靶向氮芥的DNA烷基化杂种。作为此类分子的首例，它们在体外和体内均显示出显着增强的抗癌活性，且毒性低。这项概念验证研究为开发新型有效的免疫疗法治疗癌症迈出了关键的一步。
• Coronarin D Conjugated to Methylene Homologues of Chlorambucil: Synthesis and Evaluation of their Cytotoxicity
  作者：Nisachon Khunnawutmanotham、Nitirat Chimnoi、Wattanachai Champathong、Pradit Lerdsirisuk、Theeraphon Khotmor、Supanna Techasakul

  DOI：10.3184/174751912x13362343090928

  日期：2012.6

  Methylene homologues of chlorambucil were synthesised and conjugated to the labdane diterpene coronarin D. The products were evaluated for their in vitro cytotoxicity, and were found to exhibit selective activity against MOLT-3 cell line. Two homologues of chlorambucil showed a comparable cytotoxic effect to their parent. However, as compared with the non-derivatised chlorambucil and its homologues, their conjugation with coronarin D through ester linkage did not enhance in vitro cytotoxicity against the tested cancer cell lines.

  合成了氯丁嘧啶的亚甲基同系物，并将其与唇烃二萜冠醚萜 D 共轭。对这些产品进行了体外细胞毒性评估，发现它们对 MOLT-3 细胞系具有选择性活性。氯霉素的两种同系物显示出与其母体相当的细胞毒性作用。不过，与未减活化的氯丁氨嘧啶及其同系物相比，它们通过酯键与冠突散囊菌素 D 共轭并没有增强对受测癌细胞株的体外细胞毒性。