4-(bis(2-chloroethyl)amino)phenylboronic acid | 1422986-68-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(bis(2-chloroethyl)amino)phenylboronic acid
• 英文别名: [4-[Bis(2-chloroethyl)amino]phenyl]boronic acid；[4-[bis(2-chloroethyl)amino]phenyl]boronic acid
• CAS: 1422986-68-2
• 化学式: C₁₀H₁₄BCl₂NO₂
• 分子量: 261.944
• InChiKey: LZEQTESLCCMTQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.65
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(bis(2-chloroethyl)amino)phenylboronic acid 在 双氧水 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以85%的产率得到N,N-双(2-氯乙基)-4-羟基苯胺
  参考文献：
  名称：

  Reactive Oxygen Species (ROS) Inducible DNA Cross-Linking Agents and Their Effect on Cancer Cells and Normal Lymphocytes

  摘要：

  Reducing host toxicity is one of the main challenges of cancer chemotherapy. Many tumor cells contain high levels of ROS that make them distinctively different from normal cells. We report a series of ROS-activated aromatic nitrogen mustards that selectively kill chronic lymphocytic leukemia (CLL) over normal lymphocytes. These agents showed powerful DNA cross-linking abilities when coupled with H2O2, one of the most common ROS in cancer cells, whereas little DNA cross-linking was detected without H2O2. Consistent with chemistry observation, in vitro cytotoxicity assay demonstrated that these agents induced 40-80% apoptosis in primary leukemic lymphocytes isolated from CLL patients but less than 25% cell death to normal lymphocytes from healthy donors. The IC50 for the most potent compound (2) was similar to 5 mu M in CLL cells, while the IC50 was not achieved in normal lymphocytes. Collectively, these data provide utility and selectivity of these agents that will inspire further and effective applications.

  DOI：

  10.1021/jm401349g
• 作为产物：
  描述：

  2-[(4-bromo-phenyl)-(2-hydroxy-ethyl)-amino]-ethanol 在 正丁基锂 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 4-(bis(2-chloroethyl)amino)phenylboronic acid
  参考文献：
  名称：

  Reactive Oxygen Species (ROS) Inducible DNA Cross-Linking Agents and Their Effect on Cancer Cells and Normal Lymphocytes

  摘要：

  Reducing host toxicity is one of the main challenges of cancer chemotherapy. Many tumor cells contain high levels of ROS that make them distinctively different from normal cells. We report a series of ROS-activated aromatic nitrogen mustards that selectively kill chronic lymphocytic leukemia (CLL) over normal lymphocytes. These agents showed powerful DNA cross-linking abilities when coupled with H2O2, one of the most common ROS in cancer cells, whereas little DNA cross-linking was detected without H2O2. Consistent with chemistry observation, in vitro cytotoxicity assay demonstrated that these agents induced 40-80% apoptosis in primary leukemic lymphocytes isolated from CLL patients but less than 25% cell death to normal lymphocytes from healthy donors. The IC50 for the most potent compound (2) was similar to 5 mu M in CLL cells, while the IC50 was not achieved in normal lymphocytes. Collectively, these data provide utility and selectivity of these agents that will inspire further and effective applications.

  DOI：

  10.1021/jm401349g

文献信息

• ANTI-CANCER AGENTS
  申请人：Peng Xiaohua

  公开号：US20130045949A1

  公开（公告）日：2013-02-21

  Described herein are compounds that may be selectively activated to produce active anti-cancer agents in tumor cells. Also disclosed are pharmaceutical compositions comprising the compounds, and methods of treating cancer using the compounds.

  本文描述了一些化合物，这些化合物可以被选择性地激活，以在肿瘤细胞中产生活性抗癌剂。还公开了包括这些化合物的药物组合物，以及使用这些化合物治疗癌症的方法。
• Discovery and Optimization of Novel Hydrogen Peroxide Activated Aromatic Nitrogen Mustard Derivatives as Highly Potent Anticancer Agents
  作者：Wenbing Chen、Heli Fan、Kumudha Balakrishnan、Yibin Wang、Huabing Sun、Yukai Fan、Varsha Gandhi、Leggy A. Arnold、Xiaohua Peng

  DOI：10.1021/acs.jmedchem.8b00559

  日期：2018.10.25

  We describe several new aromatic nitrogen mustards with various aromatic substituents and boronic esters that can be activated with H2O2 to efficiently cross-link DNA. In vitro studies demonstrated the anticancer potential of these compounds at lower concentrations than those of other clinically used chemotherapeutics, such as melphalan and chlorambucil. In particular, compound 10, bearing an amino

  我们描述了几种带有各种芳香族取代基和硼酸酯的新型芳香氮芥子，它们可以被H 2 O 2活化以有效地交联DNA。体外研究表明，与其他临床使用的化疗药物（例如美法仑和苯丁酸氮芥）相比，这些化合物的抗癌潜力较低。特别地，带有氨基酸酯链的化合物10对固有具有高水平活性氧物质的乳腺癌和白血病细胞具有选择性的细胞毒性。重要的是，10是10-14倍美法仑和苯丁酸氮芥对三阴性乳腺癌（TNBC）细胞更有效。同样，10与苯丁酸氮芥或先导化合物相比，对原发性慢性淋巴细胞白血病的毒性更大9。氨基酸侧链的引入提高了10的溶解度和渗透性。此外，10抑制异种移植小鼠中TNBC肿瘤的生长，而没有明显的一般毒性迹象，使该化合物成为临床开发的理想候选药物。