水杨酸己酯 | 6259-79-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 水杨酸己酯
• 英文名称: 4-[bis-(2-chloro-ethyl)-amino]-benzoic acid ethyl ester
• 英文别名: 4-[Bis-(2-chlor-aethyl)-amino]-benzoesaeure-aethylester；4--benzoesaeure-aethylester；N,N-(Bis-<2-chlor-aethyl>-4-amino-benzoesaeure-aethylester；N,N-Bis-<2-chlor-aethyl>-p-amino-benzoesaeure-aethylester；Ethyl 4-[bis(2-chloroethyl)amino]benzoate
• CAS: 6259-79-6
• 化学式: C₁₃H₁₇Cl₂NO₂
• 分子量: 290.189
• InChiKey: CLYFTZQFYMKQBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 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：

  水杨酸己酯 在 盐酸 作用下， 以 水 为溶剂， 反应 12.0h， 生成 苯丁酸氮芥
  参考文献：
  名称：

  新型enmein型二萜类杂化物与氮芥末结合：有望用于抗癌治疗药物的合成。

  摘要：

  天然来源的半球蛋白型二萜类化合物对多种人类癌细胞具有细胞毒性。然而，它们的医学应用受到化学疗法效力不足的阻碍。因此，设计并合成了一系列新型的烯醇式二萜类杂种与氮芥类，以增加抗肿瘤功效，同时降低全身毒性。大多数缀合物比亲本二萜和氮芥具有更强的抗增殖活性，特别是对于具有多重耐药性的肿瘤细胞系Bel-7402 / 5-FU。其中，化合物E2在人白血病HL-60细胞，人前列腺癌PC-3细胞，人肝癌Bel-7402细胞和耐药性人肝癌Bel-7402 / 5-FU细胞中表现出最强的抑制活性。 IC50值分别为7.83μM，3.97μM，0.77μM和2.07μM。另外，还从L-02人正常肝细胞和Bel-7402恶性肝细胞之间的细胞毒性评估中观察到选择性指数超过130的高选择性。作用机理的进一步研究表明，E2诱导Bel-7402肝癌细胞凋亡和G1期细胞周期停滞。此外，线粒体途径的功能障碍也与E2启动的细

  DOI：

  10.1016/j.ejmech.2018.01.069
• 作为产物：
  描述：

  4-[二(2-羟基乙基)氨基]-苯甲酸乙酯 在 phosphorus (III) oxychloride 作用下， 生成 水杨酸己酯
  参考文献：
  名称：

  雄烯肟肟氮芥子气生物共轭物的合成作为有效的抗肿瘤药。

  摘要：

  在本研究中，首次报道了各种甾族肟的苯乙酸和苯甲酸氮芥子气共轭物的合成和抗肿瘤活性。通过更稳定的肟酯键实现缀合，并在各种人类癌细胞系上体外评估所得新合成的缀合物的细胞毒性。通过体外比色4-（对硝基苄基）吡啶（NBP）测定法研究了其烷基化活性的程度。17E-甾族肟-苯甲酸芥末酯3β-乙酰氧基-17E- [对-（N，N-双（2-氯乙基）氨基）]苯甲酰氧基亚氨基-雄烯基-5-烯（8）成为最有效的偶联物，具有对大多数NCI 60细胞株具有明显的细胞毒性。在IGROV1卵巢癌细胞系中观察到杰出的生长抑制，GI50 = 0.937µM。一般来说，

  DOI：

  10.1016/j.steroids.2017.04.005

文献信息

• 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。
• Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity
  作者：Jianan Sun、Jiahui Mu、Shenglin Wang、Cai Jia、Dahong Li、Huiming Hua、Hao Cao

  DOI：10.1080/14756366.2021.2018685

  日期：2022.12.31

  scaffolds for antitumor activity, which promotes the development of candidate drugs with better activity. In this study, a series of nitrogen mustard derivatives of chromone were designed and synthesised, in order to discover promising anti-breast tumour candidates. Almost all target derivatives showed antiproliferative activity against MCF-7 and MDA-MB-231 cell lines. In particular, methyl (S)-3-(4-(

  摘要 Chromone已成为抗肿瘤活性最重要的合成支架之一，它促进了具有更好活性的候选药物的开发。在这项研究中，设计和合成了一系列色酮的氮芥衍生物，以发现有前景的抗乳腺癌候选药物。几乎所有靶标衍生物都显示出对 MCF-7 和 MDA-MB-231 细胞系的抗增殖活性。特别地，甲基 ( S )-3-(4-(双(2-氯乙基)氨基)苯基)-2-(5-(((6-methoxy-4-oxo-4 H -chromen-3-yl)甲基）氨基）-5-氧代戊酰胺）丙酸酯显示出最有效的抗增殖活性，IC 50值分别为 1.83 和 1.90 μM，并且在肿瘤细胞和正常细胞之间也表现出一定的选择性。对 MDA-MB-231 细胞的进一步机制探索表明，它可能通过产生细胞内 ROS 和激活 DNA 损伤来诱导 G2/M 期阻滞和细胞凋亡。此外，它还抑制MDA-MB-231细胞的转移、侵袭和粘附。总体而言，甲基 ( S
• Novel Hybrids of Natural Oridonin-Bearing Nitrogen Mustards as Potential Anticancer Drug Candidates
  作者：Shengtao Xu、Lingling Pei、Chengqian Wang、Yun-Kai Zhang、Dahong Li、Hequan Yao、Xiaoming Wu、Zhe-Sheng Chen、Yijun Sun、Jinyi Xu

  DOI：10.1021/ml500141f

  日期：2014.7.10

  A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells.
• 420. Aryl-2-halogenoalkylamines. Part II
  作者：J. L. Everett、W. C. J. Ross

  DOI：10.1039/jr9490001972

  日期：——
• 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.