(S)-6,7-dimethoxy-3-((R)-4-methoxy-9-(4-methoxyphenyl)-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)isobenzofuran-1(3H)-one | 946068-67-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 邻苯二甲酸异喹啉类
• 英文名称: (S)-6,7-dimethoxy-3-((R)-4-methoxy-9-(4-methoxyphenyl)-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)isobenzofuran-1(3H)-one
• 英文别名: 9'-(4-methoxyphenyl)-noscapine；6,7-Dimethoxy-3-[4-methoxy-9-(4-methoxyphenyl)-6-methyl-2H,5H,6H,7H,8H-[1,3]dioxolo[4,5-G]isoquinolin-5-YL]-1,3-dihydro-2-benzofuran-1-one；(3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-9-(4-methoxyphenyl)-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-3H-2-benzofuran-1-one
• CAS: 946068-67-3
• 化学式: C₂₉H₂₉NO₈
• 分子量: 519.551
• InChiKey: JVROIIDKCBXIGB-RPWUZVMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  84.9
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  诺司卡品 盐酸盐 水合物 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 氢溴酸 、 溴 、 caesium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 生成 (S)-6,7-dimethoxy-3-((R)-4-methoxy-9-(4-methoxyphenyl)-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)isobenzofuran-1(3H)-one
  参考文献：
  名称：

  一种那可汀衍生物及其制备方法和应用

  摘要：

  本发明涉及一类具有式Ⅰ结构通式的那可汀(Noscapine)衍生物及其制备方法和应用，其中衍生物中的R取代基为芳基、杂环基团、烷基、烷基羧酸或烷基酰胺。通过对那可汀母环结构进行化学修饰、引入官能团以增强其抗癌活性而获得活性高、副作用低的抗癌药物。

  公开号：

  CN105801588B

文献信息

• 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。
• Novel 9′-substituted-noscapines: Synthesis with Suzuki cross-coupling, structure elucidation and biological evaluation
  作者：Elena Porcù、Attila Sipos、Giuseppe Basso、Ernest Hamel、Ruoli Bai、Verena Stempfer、Antal Udvardy、Attila Cs. Bényei、Helmut Schmidhammer、Sándor Antus、Giampietro Viola

  DOI：10.1016/j.ejmech.2014.07.050

  日期：2014.9

  Tubulin is a major molecular target for anticancer drugs. The dynamic process of microtubule assembly and disassembly can be blocked by various agents that bind to distinct sites on tubulin, usually its β-subunit. Among the antimitotic agents that perturb microtubule dynamics, noscapinoids represent an emerging class of agents. In particular, 9'-bromonoscapine (EM011) has been identified as a potent noscapine analog. Here we present high yielding, efficient synthetic methods based on Suzuki coupling of 9'-alkyl and 9'-arylnoscapines and an evaluation of their antiproliferative properties. Our results showed that 9'-alkyl and 9'-aryl derivatives inhibit proliferation of human cancer cells. The most active compounds were the 9'-methyl and the 9'-phenyl derivatives, which showed similar cytotoxic potency in comparison to the 9'-brominated derivative. Interestingly these newly synthesized derivatives did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. All of these derivatives, except 9'-(2-methoxyphenyl)-noscapine, efficiently induced a cell cycle arrest in the G2/M phase of the cell cycle in HeLa and Jurkat cells. Furthermore, we showed that the most active compounds in HeLa cells induced apoptosis following the mitochondrial pathway with the activation of both caspase-9 and caspase-3. In addition, these compounds significantly reduced the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2.
• 一种那可汀衍生物及其制备方法和应用
  申请人：长沙凯得尔森生物技术有限公司

  公开号：CN105801588B

  公开（公告）日：2018-09-18

  本发明涉及一类具有式Ⅰ结构通式的那可汀(Noscapine)衍生物及其制备方法和应用，其中衍生物中的R取代基为芳基、杂环基团、烷基、烷基羧酸或烷基酰胺。通过对那可汀母环结构进行化学修饰、引入官能团以增强其抗癌活性而获得活性高、副作用低的抗癌药物。