6,7-dimethoxy-3-(4-methoxy-6-methyl-9-p-tolyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl)isobenzofuran-1(3H)-one | 946068-66-2

• 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: 6,7-dimethoxy-3-(4-methoxy-6-methyl-9-p-tolyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl)isobenzofuran-1(3H)-one
• 英文别名: 9'-(4-methylphenyl)-noscapine；(3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-6-methyl-9-(4-methylphenyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-3H-2-benzofuran-1-one
• CAS: 946068-66-2
• 化学式: C₂₉H₂₉NO₇
• 分子量: 503.552
• InChiKey: JTHRHOZIDJQLSO-RPWUZVMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  75.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-甲苯硼酸 、 9-bromonoscapine 在 1-(2-吡啶基)苯并三唑 、 palladium diacetate 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 6.0h， 以72%的产率得到6,7-dimethoxy-3-(4-methoxy-6-methyl-9-p-tolyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl)isobenzofuran-1(3H)-one
  参考文献：
  名称：

  2-（1-苯并三唑基）吡啶：钯催化的CC（铃木，Heck，藤原茂森，Sonogashira），CN和CS偶联反应的稳健双齿配体

  摘要：

  设计了一种新型的双齿配体1-（吡啶-2-基）-1 H-苯并[ d ] [1,2,3]三唑，并用于钯催化的CC（Suzuki，Heck，Fujiwara– Moritani和Sonogashira），CN和CS偶联反应。发现该配体便宜，热稳定，易于以几克规模由容易获得的起始原料合成，显示出使用简单性和在应用中的坚固性，从而使该配体对于不同的偶联反应有效。适当地，苯并三唑环的NN键的供体能力和吡啶环的N上的孤对电子增强了配体的二齿能力。

  DOI：

  10.1002/adsc.201200583

文献信息

• 2-(1-Benzotriazolyl)pyridine: A Robust Bidentate Ligand for the Palladium-Catalyzed CC (Suzuki, Heck, Fujiwara-Moritani, Sonogashira), CN and CS Coupling Reactions
  作者：Akhilesh K. Verma、Rajeev R. Jha、Ritu Chaudhary、Rakesh K. Tiwari、Abhinandan K. Danodia

  DOI：10.1002/adsc.201200583

  日期：2013.2.1

  designed and employed for the palladium-catalyzed CC (Suzuki, Heck, Fujiwara–Moritani, and Sonogashira), CN and CS coupling reactions. The ligand was found to be inexpensive, thermally stable, easy to synthesize from easily accessible starting materials on a multigram scale, show simplicity in use, and robustness in application, making this ligand effective for different coupling reactions. Suitably, the

  设计了一种新型的双齿配体1-（吡啶-2-基）-1 H-苯并[ d ] [1,2,3]三唑，并用于钯催化的CC（Suzuki，Heck，Fujiwara– Moritani和Sonogashira），CN和CS偶联反应。发现该配体便宜，热稳定，易于以几克规模由容易获得的起始原料合成，显示出使用简单性和在应用中的坚固性，从而使该配体对于不同的偶联反应有效。适当地，苯并三唑环的NN键的供体能力和吡啶环的N上的孤对电子增强了配体的二齿能力。
• 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.