2-bromoethyl-2-(6-methoxylnaphthyl-2-ene)propanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-bromoethyl-2-(6-methoxylnaphthyl-2-ene)propanoate
• 英文别名: 2-bromoethyl 2-(6-methoxynaphthalen-2-yl)propanoate
• 化学式: C₁₆H₁₇BrO₃
• 分子量: 337.213
• InChiKey: XCRYNNAPVZKWDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromoethyl-2-(6-methoxylnaphthyl-2-ene)propanoate 在 水 、 sodium hydroxide 作用下， 以81.2 %的产率得到2-(6-甲氧基-2-萘基)丙酸
  参考文献：
  名称：

  一种D，L-萘普生的制备方法

  摘要：

  本发明涉及一种D，L‑萘普生的制备方法，属于药物合成技术领域。为了解决现有的污染大且需额外添加重排催化剂的问题，提供一种D，L‑萘普生的制备方法，包括将6‑甲氧基‑2‑丙酰萘、二元醇和卤化铜加入在沸点高于100℃的非水溶性有机溶剂中并在回流条件下进行回流反应，回流反应的过程中分离出反应产生的水分，反应至不产生水分之后，降温至80℃～100℃进行保温反应，得到重排反应中间体酯化物；在碱金属氢氧化物的水溶液作用下进行水解反应，然后再进行酸化，得到产物D,L‑萘普生。本发明无需额外添加重排催化剂，减少对环境的污染，具有对环境友好的优点，且操作更便捷，具有产物收率高的优点。

  公开号：

  CN117534557A
• 作为产物：
  描述：

  2-(6-甲氧基-2-萘基)丙酸 、 2-溴乙醇 在 氯化亚砜 作用下， 生成 2-bromoethyl-2-(6-methoxylnaphthyl-2-ene)propanoate
  参考文献：
  名称：

  Synthesis and Evaluation of Novel Erlotinib–NSAID Conjugates as More Comprehensive Anticancer Agents

  摘要：

  A series of novel anticancer agents were designed and synthesized based on coupling of different nonsteroidal anti-inflammatory drugs (NSAIDs) with the epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib. Both the antiproliferative and pharmacokinetic activity of the target compounds were evaluated using HCC827 and A431 tumor cell lines. Among the derivatives made, compounds 10a, 10c, and 21g showed superb potency, comparable to that of erlotinib. Furthermore, preliminary SAR analysis showed that when the NSAIDs were conjugated via linkage to C-6 OH versus linkage to C-7 OH of the quinazoline nucleus, superior anticancer activity was achieved. Finally, the in vitro pharmacokinetic profile of several conjugates demonstrated the desired dissociation kinetics as the coupled molecules were effectively hydrolyzed, releasing both erlotinib and the specific NSAID in a time-dependent manner. The conjugation strategy represents a unique and simplified approach toward combination therapy, particularly for the treatment of cancers where both EGFR overexpression and inflammation play a direct role in disease progression.

  DOI：

  10.1021/acsmedchemlett.5b00286

文献信息

• COUPLING COMPOUNDS OF NSAID ANTI-INFLAMMATORY AND ANALGESIC DRUGS AND EGFR KINASE INHIBITORS, SYNTHESIS METHODS AND APPLICATIONS THEREOF
  申请人：Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

  公开号：US20160175453A1

  公开（公告）日：2016-06-23

  The present invention discloses coupling compounds of a structure as shown in Formula I, II or III formed by connecting NSAID anti-inflammatory and analgesic drugs and EGFR inhibitors by ester bonds or pharmaceutically acceptable salts or stereoisomers thereof or prodrug molecules thereof: where R is a NSAID anti-inflammatory and analgesic drug. In the present invention, the coupling compounds obtained by coupling NSAID anti-inflammatory and analgesic drugs with EGFR inhibitors have excellent therapeutic effects of tumors and provide new drugs for clinic treatment options.

  本发明揭示了一种结构如公式I、II或III所示的偶联化合物，通过酯键或药用可接受的盐或其立体异构体或其前药分子连接非甾体类抗炎镇痛药和EGFR抑制剂而形成：其中R为非甾体类抗炎镇痛药。在本发明中，通过将非甾体类抗炎镇痛药与EGFR抑制剂偶联而获得的偶联化合物具有出色的肿瘤治疗效果，并为临床治疗提供了新的药物选择。
• A General Electron Donor–Acceptor Photoactivation Platform of Diaryliodonium Reagents: Arylation of Heterocycles
  作者：Prahallad Meher、Satya Prakash Panda、Sanat Kumar Mahapatra、Karan Ramdas Thombare、Lisa Roy、Sandip Murarka

  DOI：10.1021/acs.orglett.3c03365

  日期：2023.11.24

  photoredox system comprising sodium iodide, triphenyl phosphine, and N,N,N′,N′-tetramethylethylenediamine (TMEDA) that can form a self-assembled tetrameric electron donor–acceptor (EDA) complex with diaryliodonium reagents (DAIRs) and furnish aryl radicals upon visible light irradiation. This practical mode of activation of DAIRs enables arylation of an array of heterocycles under mild conditions to provide

  我们报道了一种由碘化钠、三苯基膦和N , N , N ', N'-四甲基乙二胺 (TMEDA) 组成的光氧化还原系统，该系统可以与二芳基碘试剂 (DAIR) 形成自组装的四聚体电子供体-受体 (EDA) 复合物，在可见光照射下提供芳基自由基。这种 DAIR 激活的实用模式能够在温和条件下对一系列杂环进行芳基化，从而以中等至优异的产率提供相应的杂芳基-（杂）芳基组装。包括光物理和 DFT 研究在内的详细机制研究提供了对反应机制的深入了解。
• US9452220B2
  申请人：——

  公开号：US9452220B2

  公开（公告）日：2016-09-27
• Synthesis and Evaluation of Novel Erlotinib–NSAID Conjugates as More Comprehensive Anticancer Agents
  作者：Yanmei Zhang、Micky D. Tortorella、Jinxi Liao、Xiaochu Qin、Tingting Chen、Jinfeng Luo、Jiantong Guan、John J. Talley、Zhengchao Tu

  DOI：10.1021/acsmedchemlett.5b00286

  日期：2015.10.8

  A series of novel anticancer agents were designed and synthesized based on coupling of different nonsteroidal anti-inflammatory drugs (NSAIDs) with the epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib. Both the antiproliferative and pharmacokinetic activity of the target compounds were evaluated using HCC827 and A431 tumor cell lines. Among the derivatives made, compounds 10a, 10c, and 21g showed superb potency, comparable to that of erlotinib. Furthermore, preliminary SAR analysis showed that when the NSAIDs were conjugated via linkage to C-6 OH versus linkage to C-7 OH of the quinazoline nucleus, superior anticancer activity was achieved. Finally, the in vitro pharmacokinetic profile of several conjugates demonstrated the desired dissociation kinetics as the coupled molecules were effectively hydrolyzed, releasing both erlotinib and the specific NSAID in a time-dependent manner. The conjugation strategy represents a unique and simplified approach toward combination therapy, particularly for the treatment of cancers where both EGFR overexpression and inflammation play a direct role in disease progression.
• 一种D，L-萘普生的制备方法
  申请人：江苏八巨药业有限公司

  公开号：CN117534557A

  公开（公告）日：2024-02-09

  本发明涉及一种D，L‑萘普生的制备方法，属于药物合成技术领域。为了解决现有的污染大且需额外添加重排催化剂的问题，提供一种D，L‑萘普生的制备方法，包括将6‑甲氧基‑2‑丙酰萘、二元醇和卤化铜加入在沸点高于100℃的非水溶性有机溶剂中并在回流条件下进行回流反应，回流反应的过程中分离出反应产生的水分，反应至不产生水分之后，降温至80℃～100℃进行保温反应，得到重排反应中间体酯化物；在碱金属氢氧化物的水溶液作用下进行水解反应，然后再进行酸化，得到产物D,L‑萘普生。本发明无需额外添加重排催化剂，减少对环境的污染，具有对环境友好的优点，且操作更便捷，具有产物收率高的优点。