9-Chloro-Noscapine | 887497-12-3

• 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: 9-Chloro-Noscapine
• 英文别名: (S)-3-((R)-9-chloro-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxyisobenzofuran-1(3H)-one；1(3H)-Isobenzofuranone, 3-((5R)-9-chloro-5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo(4,5-g)isoquinolin-5-yl)-6,7-dimethoxy-, (3S)-；(3S)-3-[(5R)-9-chloro-4-methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-6,7-dimethoxy-3H-2-benzofuran-1-one
• CAS: 887497-12-3
• 化学式: C₂₂H₂₂ClNO₇
• 分子量: 447.872
• InChiKey: WUWCRDPPBSLSLD-SJORKVTESA-N

物化性质

• 熔点：
  169.0-169.1 °C
• 沸点：
  586.4±50.0 °C(Predicted)
• 密度：
  1.390±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 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：

  那可汀 在 磺酰氯 作用下， 以 氯仿 为溶剂， 反应 10.0h， 以90%的产率得到9-Chloro-Noscapine
  参考文献：
  名称：

  Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death

  摘要：

  We have previously identified the naturally occurring non-toxic antitussive phthalideiso-quinoline alkaloid, noscapine as a tubulin-binding agent that arrests mitosis and induces apoptosis. Here we present high-yield efficient synthetic methods and an evaluation of anticancer activity of halogenated noscapine analogs. our results show that all analogs display higher tubulin-binding activity than noscapine and inhibit proliferation of human cancer cells (MCF-7, MDA-MB-231 and CEM). Surprisingly, the bromo-analog is similar to 40-fold more potent than noscapine in inhibiting cellular proliferation of MCF-7 cells. The ability of these analogs to inhibit cellular proliferation is mediated by cell cycle arrest at the G(2)/M phase, in that all analogs except 9-iodonoscapine, caused selective mitotic arrest with a higher efficiency than noscapine followed by apoptotic cell death as shown by immunofluorescence and quantitative FACS analyses. Furthermore, our results reveal the appearance of numerous fragmented nuclei as evidenced by DAPI staining. Thus, our data indicate a great potential of these compounds for studying microtubule-mediated processes and as chemotherapeutic agents for the management of human cancers. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2006.05.004
• 作为试剂：
  描述：

  那可汀 、 磺酰氯 、 甲醇 、 水 在 氯仿 、 Brine 、 magnesium sulfate 、 crude product 、 9-Chloro-Noscapine 作用下， 以 氯仿 为溶剂， 反应 11.0h， 以afforded the desired product, (S)-3-((R)-9-chloro-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-6,7-dimethoxyisobenzofuran-1(3H)-one (4)的产率得到9-Chloro-Noscapine
  参考文献：
  名称：

  9-CHLORO NOSCAPINE AND ITS USE IN TREATING CANCERS, INCLUDING DRUG-RESISTANT CANCERS

  摘要：

  本文介绍了9-氯-诺斯，其前药以及其药物可接受的盐。还介绍了包括9-氯-诺斯的药物组合物以及其制备和使用方法。9-氯-诺斯是一种诺斯卡平类似物，可以通过结合微管蛋白并选择性诱导凋亡，在药物耐药性癌症（卵巢癌和T细胞淋巴瘤）中治疗和/或预防各种癌症。9-氯-诺斯可以通过有丝分裂阻滞干扰细胞周期的进程，随后出现与增加的caspase-3活化和TUNEL阳性细胞相关的细胞凋亡。因此，9-氯-诺斯是一种新型治疗剂，可用于治疗各种癌症，包括卵巢癌和T细胞淋巴瘤癌，即使这些癌症已经对目前可用的化疗药物产生了耐药性。

  公开号：

  US20100249172A1

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。
• CONJUGATES OF NOSCAPINE AND FOLIC ACID AND THEIR USE IN TREATING CANCER
  申请人：Joshi Harish C.

  公开号：US20110286919A1

  公开（公告）日：2011-11-24

  The present invention is directed to compounds which are conjugates of two non-toxic natural products, noscapine (and various noscapine analogs) and folic acid (and various folic acid analogs), where the folic acid is conjugated to noscapine or the noscapine analog at the 9-position on the isoquinoline ring on the noscapine framework. Pharmaceutical compositions including the compounds, and methods of treating various tumors using the compounds and compositions, are also disclosed. The conjugates are particularly useful for treating cancers which overexpress the Folate Receptor α (FRa) receptor.

  本发明涉及两种非毒性天然产物，诺斯卡平（及各种诺斯卡平类似物）和叶酸（及各种叶酸类似物）的结合物，其中叶酸与诺斯卡平或诺斯卡平类似物在诺斯卡平框架上的异喹啉环的9位结合。还公开了包括该化合物的制药组合物以及使用该化合物和组合物治疗各种肿瘤的方法。这些结合物特别适用于治疗过度表达叶酸受体α（FRa）受体的癌症。
• WO2008/109614
  申请人：——

  公开号：——

  公开（公告）日：——
• NOSCAPINE AND NOSCAPINE ANALOGS AND THEIR USE IN TREATING INFECTIOUS DISEASES BY TUBULIN BINDING INHIBITION
  申请人：Emory University

  公开号：EP2328578A2

  公开（公告）日：2011-06-08
• US8426398B2
  申请人：——

  公开号：US8426398B2

  公开（公告）日：2013-04-23