(R)-9-bromo-5-((S)-4,5-dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo[4,5-g]isoquinoline | 565418-40-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (R)-9-bromo-5-((S)-4,5-dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo[4,5-g]isoquinoline
• 英文别名: (R)-9-bromo-5-((S)-4,5-dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline；1,3-dihydro-4,5-dimethoxy-1-[1,2,3,4-tetrahydro-5-bromo-8-methoxy-2-methyl-6,7-methylendioxyisoquinolyl-1]isobenzofuran；EM012；reduced 5-bromonoscapine；1,3-Dioxolo(4,5-g)isoquinoline, 9-bromo-5-((1S)-1,3-dihydro-4,5-dimethoxy-1-isobenzofuranyl)-5,6,7,8-tetrahydro-4-methoxy-6-methyl-, (5R)-；(5R)-9-bromo-5-[(1S)-4,5-dimethoxy-1,3-dihydro-2-benzofuran-1-yl]-4-methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinoline
• CAS: 565418-40-8
• 化学式: C₂₂H₂₄BrNO₆
• 分子量: 478.34
• InChiKey: VVSDXCUYQGHQTE-MJGOQNOKSA-N

物化性质

• 沸点：
  546.7±50.0 °C(Predicted)
• 密度：
  1.449±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-9-bromo-5-((S)-4,5-dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo[4,5-g]isoquinoline 在 Amberlyst-A 26 fluoride form 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以72%的产率得到(5R)-5-[(1S)-4,5-dimethoxy-1,3-dihydro-2-benzofuran-1-yl]-9-fluoro-4-methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinoline
  参考文献：
  名称：

  环状醚氟化Noscapine类似物的合成和生物学评估。

  摘要：

  我们在这里介绍一种新型的半合成的环醚氟化Noscapine类似物（CEFNA），在激素反应性（MCF-7）和激素反应性（MDA-MB-231）乳腺癌细胞中均显示出有效的抗增殖和抗癌活性。有趣的是，它对MCF-7细胞的阿霉素耐药变体MCF-7 / Adr也有效。免疫荧光实验显示大量微核，表明这种新型类似物触发了凋亡细胞的死亡。从机制上讲，CEFNA发挥着强大的抗有丝分裂作用，正如细胞周期研究所揭示的那样，该研究表明G2 / M群体的剂量依赖性增加先于亚G1群体的增加，提示细胞凋亡。

  DOI：

  10.1016/j.bmc.2006.09.012
• 作为产物：
  描述：

  那可汀 在 sodium tetrahydroborate 、 三氟化硼乙醚 、 氢溴酸 、 溴 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 (R)-9-bromo-5-((S)-4,5-dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-dioxolo[4,5-g]isoquinoline
  参考文献：
  名称：

  环状醚氟化Noscapine类似物的合成和生物学评估。

  摘要：

  我们在这里介绍一种新型的半合成的环醚氟化Noscapine类似物（CEFNA），在激素反应性（MCF-7）和激素反应性（MDA-MB-231）乳腺癌细胞中均显示出有效的抗增殖和抗癌活性。有趣的是，它对MCF-7细胞的阿霉素耐药变体MCF-7 / Adr也有效。免疫荧光实验显示大量微核，表明这种新型类似物触发了凋亡细胞的死亡。从机制上讲，CEFNA发挥着强大的抗有丝分裂作用，正如细胞周期研究所揭示的那样，该研究表明G2 / M群体的剂量依赖性增加先于亚G1群体的增加，提示细胞凋亡。

  DOI：

  10.1016/j.bmc.2006.09.012

文献信息

• Brominated Derivatives of Noscapine Are Potent Microtubule-interfering Agents That Perturb Mitosis and Inhibit Cell Proliferation
  作者：Jun Zhou、Kamlesh Gupta、Shefali Aggarwal、Ritu Aneja、Ramesh Chandra、Dulal Panda、Harish C. Joshi

  DOI：10.1124/mol.63.4.799

  日期：2003.4.1

  Noscapine, a microtubule-interfering agent, has been shown to arrest mitosis, to induce apoptosis, and to have potent antitumor activity. We report herein that two brominated derivatives of noscapine, 5-bromonoscapine (5-Br-nosc) and reduced 5-bromonoscapine (Rd 5-Br-nosc), have higher tubulin binding activity than noscapine and affect tubulin polymerization differently from noscapine. In addition, they are able to arrest cell cycle progression at mitosis at concentrations much lower than noscapine. Interestingly, whereas noscapine-arrested cells have nearly normal bipolar spindles, cells arrested by 5-Br-nosc and Rd 5-Br-nosc form multipolar spindles. Nevertheless, noscapine and the two derivatives all affect the attachment of chromosomes to spindle microtubules and they impair the tension across paired kinetochores to similar degrees. 5-Br-nosc and Rd 5-Br-nosc are also more active than noscapine in inhibiting the proliferation of various human cancer cells, including those that are resistant to paclitaxel and epothilone. Our results thus indicate a great potential for the use of 5-Br-nosc and Rd 5-Br-nosc both as biological tools for studying microtubule-mediated processes and as chemotherapeutic agents for the treatment of human cancers.

  去甲纳曲酮，一种微管干扰剂，已被证明能阻止有丝分裂，诱导细胞凋亡，并具有强效的抗肿瘤活性。本文报告了两种溴化的去甲纳曲酮衍生物，即5-溴去甲纳曲酮（5-Br-nosc）和还原型5-溴去甲纳曲酮（Rd 5-Br-nosc），它们与微管蛋白结合的活性高于去甲纳曲酮，并且影响微管蛋白聚合的方式与去甲纳曲酮不同。此外，它们能在比去甲纳曲酮低得多的浓度下阻止细胞周期在有丝分裂期的进展。有趣的是，尽管去甲纳曲酮阻止的细胞具有几乎正常的双极纺锤体，但5-Br-nosc和Rd 5-Br-nosc阻止的细胞形成了多极纺锤体。尽管如此，去甲纳曲酮及其两种衍生物都影响染色体与纺锤体微管的附着，并且它们对成对着丝粒间的张力损害程度相似。5-Br-nosc和Rd 5-Br-nosc在抑制多种人类癌细胞的增殖方面也比去甲纳曲酮更活跃，包括对紫杉醇和埃博霉素耐药的癌细胞。因此，我们的结果表明5-Br-nosc和Rd 5-Br-nosc具有巨大的潜力，既可作为研究微管介导过程的生物学工具，也可作为治疗人类癌症的化疗药物。
• Noscapine and Noscapine Analogs and Their Use in treating Infectious Diseases by Tubulin Binding Inhibition
  申请人：Acuff Cory

  公开号：US20110274651A1

  公开（公告）日：2011-11-10

  Compositions and methods for treating or preventing infectious diseases, and inhibiting the ability of microbes to travel within mammalian cells, and inhibiting microbial replication, are disclosed. The compositions include various noscapine analogs, which are capable of blocking the movement of viruses and other microbes within mammalian and other cells by inhibiting the cytoplasmic transport mechanisms within the cells. The compositions described herein include an effective amount of the noscapine analogues described herein, along with a pharmaceutically acceptable carrier or excipient. The compositions can also include one or more additional antimicrobial compounds.

  本发明公开了用于治疗或预防传染病、抑制微生物在哺乳动物细胞内移动和抑制微生物复制能力的组合物和方法。该组合物包括各种诺斯卡平类似物，能够通过抑制细胞内的胞质转运机制，阻止病毒和其他微生物在哺乳动物和其他细胞内移动。本发明所描述的组合物包括所述诺斯卡平类似物的有效量，以及药学上可接受的载体或赋形剂。该组合物还可以包括一个或多个额外的抗微生物化合物。
• NOSCAPINE AND ANALOGS AND METHODS RELATED THERETO
  申请人：Zughaier Susu

  公开号：US20120053199A1

  公开（公告）日：2012-03-01

  The invention relates to the innate immune pathway and anti-inflammatory molecules with therapeutic properties. In some embodiments, the invention relates to compounds and pharmaceutical compositions and methods of using the compounds and compositions to treat inflammatory diseases including inflammation associated with auto-immune diseases.
• US8841317B2
  申请人：——

  公开号：US8841317B2

  公开（公告）日：2014-09-23
• Synthesis and biological evaluation of a cyclic ether fluorinated noscapine analog
  作者：Ritu Aneja、Surya N. Vangapandu、Harish C. Joshi

  DOI：10.1016/j.bmc.2006.09.012

  日期：2006.12

  We present here a novel semi-synthetic cyclic ether fluorinated noscapine analog (CEFNA) that shows potent antiproliferative and anticancer activity in both hormone-responsive (MCF-7) and hormone non-responsive (MDA-MB-231) breast cancer cells. Interestingly, it is also effective against MCF-7/Adr, an adriamycin-resistant variant of MCF-7 cells. Immunofluorescence experiments showed numerous micronuclei

  我们在这里介绍一种新型的半合成的环醚氟化Noscapine类似物（CEFNA），在激素反应性（MCF-7）和激素反应性（MDA-MB-231）乳腺癌细胞中均显示出有效的抗增殖和抗癌活性。有趣的是，它对MCF-7细胞的阿霉素耐药变体MCF-7 / Adr也有效。免疫荧光实验显示大量微核，表明这种新型类似物触发了凋亡细胞的死亡。从机制上讲，CEFNA发挥着强大的抗有丝分裂作用，正如细胞周期研究所揭示的那样，该研究表明G2 / M群体的剂量依赖性增加先于亚G1群体的增加，提示细胞凋亡。