5-[(Z)-2-[3-(3-bromopropoxy)-4-methoxyphenyl]ethenyl]-1,2,3-trimethoxybenzene | 1434133-49-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 5-[(Z)-2-[3-(3-bromopropoxy)-4-methoxyphenyl]ethenyl]-1,2,3-trimethoxybenzene
• CAS: 1434133-49-9
• 化学式: C₂₁H₂₅BrO₅
• 分子量: 437.331
• InChiKey: CMGLPMFRUKJDEN-SREVYHEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[(Z)-2-[3-(3-bromopropoxy)-4-methoxyphenyl]ethenyl]-1,2,3-trimethoxybenzene 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 1-[3-[2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]propyl]piperazine
  参考文献：
  名称：

  Site-Specific and Far-Red-Light-Activatable Prodrug of Combretastatin A-4 Using Photo-Unclick Chemistry

  摘要：

  Although tissue-penetrable light (red and NIR) has great potential for spatiotemporally controlled release of therapeutic agents, it has been hampered because of the lack of chemistry translating the photonic energy to the cleavage of a chemical bond. Recently, we discovered that an aminoacrylate group could be cleaved to release parent drugs after oxidation by SO and have called this "photo-unclick chemistry". We demonstrate its application to far-red-light-activated prodrugs. A prodrug of combretastatin A-4 (CA4) was prepared, CMP-L-CA4, where CMP is dithiaporphyrin, a photosensitizer, and L is an aminoacrylate linker. Upon irradiation with 690 nm diode laser, the aminoacrylate linker of the prodrug was cleaved, rapidly releasing CA4 (>80% in 10 min) in CDCl3. In tissue culture, it showed about a 6-fold increase in its IC50 in MCF-7 after irradiation, most likely because of the released CA4. Most significantly, CMP-L-CA4 had better antitumor efficacy in vivo than its noncleavable (NC) analog, CMP-NCL-CA4. This is the first demonstration of the in vivo efficacy of the novel low-energy-light-activatable prodrug using the photo-unclick chemistry.

  DOI：

  10.1021/jm400139w
• 作为产物：
  描述：

  (Z)-3,4,5,4',-四甲氧基-3'-羟基二苯乙烯 、 1,3-二溴丙烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以84%的产率得到5-[(Z)-2-[3-(3-bromopropoxy)-4-methoxyphenyl]ethenyl]-1,2,3-trimethoxybenzene
  参考文献：
  名称：

  Site-Specific and Far-Red-Light-Activatable Prodrug of Combretastatin A-4 Using Photo-Unclick Chemistry

  摘要：

  Although tissue-penetrable light (red and NIR) has great potential for spatiotemporally controlled release of therapeutic agents, it has been hampered because of the lack of chemistry translating the photonic energy to the cleavage of a chemical bond. Recently, we discovered that an aminoacrylate group could be cleaved to release parent drugs after oxidation by SO and have called this "photo-unclick chemistry". We demonstrate its application to far-red-light-activated prodrugs. A prodrug of combretastatin A-4 (CA4) was prepared, CMP-L-CA4, where CMP is dithiaporphyrin, a photosensitizer, and L is an aminoacrylate linker. Upon irradiation with 690 nm diode laser, the aminoacrylate linker of the prodrug was cleaved, rapidly releasing CA4 (>80% in 10 min) in CDCl3. In tissue culture, it showed about a 6-fold increase in its IC50 in MCF-7 after irradiation, most likely because of the released CA4. Most significantly, CMP-L-CA4 had better antitumor efficacy in vivo than its noncleavable (NC) analog, CMP-NCL-CA4. This is the first demonstration of the in vivo efficacy of the novel low-energy-light-activatable prodrug using the photo-unclick chemistry.

  DOI：

  10.1021/jm400139w

文献信息

• Multifunctional Molecular Therapeutic Agent for Targeted and Controlled Dual Chemo- and Photodynamic Therapy
  作者：Summer Y. Y. Ha、Yimin Zhou、Wing-Ping Fong、Dennis K. P. Ng

  DOI：10.1021/acs.jmedchem.0c00893

  日期：2020.8.13

  A novel molecular therapeutic agent was designed and synthesized, which contains three functional components, namely, a zinc(II) phthalocyanine substituted with a 2,4-dinitrobenzenesulfonate (DNBS) group as a glutathione (GSH)-activated photosensitizer, a chemo-prodrug based on combretastatin A-4 (CA4) with a singlet oxygen-cleavable aminoacrylate linker, and a biotin moiety as a tumor-targeting ligand

  设计并合成了一种新型分子治疗剂，它包含三个功能成分，即被谷胱甘肽（GSH）活化的光敏剂，被2,4-二硝基苯磺酸盐（DNBS）取代的酞菁锌（II）取代基，化学前药基于康普他汀A-4（CA4）和单线态氧可裂解的氨基丙烯酸酯连接基，以及生物素部分作为肿瘤靶向配体。与用作阴性对照的低生物素受体表达的HCT-116细胞相比，该缀合物显示出对生物素受体阳性HepG2细胞的优先摄取，从而在去除DNBS后恢复了荧光发射和产生单线态氧按细胞内GSH分组。
• Far-Red Light Activatable, Multifunctional Prodrug for Fluorescence Optical Imaging and Combinational Treatment
  作者：Moses Bio、Pallavi Rajaputra、Gregory Nkepang、Youngjae You

  DOI：10.1021/jm5000722

  日期：2014.4.24

  We recently developed "photo-unclick chemistry", a novel chemical tool involving the cleavage of aminoacrylate by singlet oxygen, and demonstrated its application to visible light-activatable prodrugs. In this study, we prepared an advanced multifunctional prodrug, Pc-(L-CA4)(2), composed of the fluorescent photosensitizer phthalocyanine (Pc), an SO-labile aminoacrylate linker (L), and a cytotoxic drug combretastatin A-4 (CA4). Pc-(L-CA4)(2) had reduced dark toxicity compared with CA4. However, once illuminated, it showed improved toxicity similar to CA4 and displayed bystander effects in vitro. We monitored the time-dependent distribution of Pc-(L-CA4)(2) using optical imaging with live mice. We also effectively ablated tumors by the illumination with far-red light to the mice, presumably through the combined effects of photodynamic therapy (PDT) and released chemotherapy drug, without any sign of acute systemic toxicity.
• Site-Specific and Far-Red-Light-Activatable Prodrug of Combretastatin A-4 Using Photo-Unclick Chemistry
  作者：Moses Bio、Pallavi Rajaputra、Gregory Nkepang、Samuel G. Awuah、Abugafar M. L. Hossion、Youngjae You

  DOI：10.1021/jm400139w

  日期：2013.5.23

  Although tissue-penetrable light (red and NIR) has great potential for spatiotemporally controlled release of therapeutic agents, it has been hampered because of the lack of chemistry translating the photonic energy to the cleavage of a chemical bond. Recently, we discovered that an aminoacrylate group could be cleaved to release parent drugs after oxidation by SO and have called this "photo-unclick chemistry". We demonstrate its application to far-red-light-activated prodrugs. A prodrug of combretastatin A-4 (CA4) was prepared, CMP-L-CA4, where CMP is dithiaporphyrin, a photosensitizer, and L is an aminoacrylate linker. Upon irradiation with 690 nm diode laser, the aminoacrylate linker of the prodrug was cleaved, rapidly releasing CA4 (>80% in 10 min) in CDCl3. In tissue culture, it showed about a 6-fold increase in its IC50 in MCF-7 after irradiation, most likely because of the released CA4. Most significantly, CMP-L-CA4 had better antitumor efficacy in vivo than its noncleavable (NC) analog, CMP-NCL-CA4. This is the first demonstration of the in vivo efficacy of the novel low-energy-light-activatable prodrug using the photo-unclick chemistry.