N-[(7S)-3-ethoxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]amine

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: N-[(7S)-3-ethoxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]amine
• 英文别名: 3-ethoxydeacetylthiocolchicine；(7S)-7-amino-3-ethoxy-1,2,-dimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]heptalene-9-one；(7S)-7-amino-3-ethoxy-1,2-dimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]-heptalen-9-one；(7S)-7-amino-3-ethoxy-1,2-dimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]heptalene-9-one；(7S)-7-amino-3-ethoxy-1,2-dimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]heptalen-9-one
• 化学式: C₂₁H₂₅NO₄S
• 分子量: 387.5
• InChiKey: OSMAXHZHGVMNNG-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  96.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(7S)-3-ethoxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]amine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 methanesulfonic acid 3-(3-ethyloxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalene-7-ylcarbamoyl)-2-fluorobenzyl ester
  参考文献：
  名称：

  METHOD FOR PREPARING TRICYCLIC DERIVATIVES

  摘要：

  本发明涉及一种制备三环衍生物的方法，更具体地，涉及一种制备高产率和纯度的三环衍生物中间体的方法，该方法包括：通过酯化和取代2-氟异苯二甲酸化合物引入一个羟基；引入一个哌啶基团；通过还原反应引入一个羟基；然后水解所得化合物，并且涉及使用该中间体制备三环衍生物的方法。根据本发明的方法，通过使用重新结晶而不是典型方法中的柱层析，可以提供高产率和经济可行性以及高纯度和收率的三环衍生物和其中间体。此外，本发明的方法可以用于工业大规模生产，因为使用的硼氢化钠或铝锂氢化物具有低火灾风险，而不像使用锂硼氢化物的典型方法那样由于火灾风险高而不适用于工业应用。

  公开号：

  US20120101296A1
• 作为产物：
  描述：

  秋水仙碱 在 盐酸 、 甲醇 、 4-二甲氨基吡啶 、 sodium methylate 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 18.0h， 生成 N-[(7S)-3-ethoxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]amine
  参考文献：
  名称：

  [EN] NOVEL COLCHICINE DERIVATIVES, METHODS AND USES THEREOF
  [FR] NOUVEAUX DÉRIVÉS DE COLCHICINE, LEURS PROCÉDÉS ET UTILISATIONS

  摘要：

  本发明涉及秋水仙碱衍生物、其制备方法及其用于治疗癌症的应用。在某些实施例中，秋水仙碱衍生物包括公式(I)的化合物，其中Z是O或S；R1选自H、卤素基团、取代或不取代的烃基团或取代或不取代的杂原子基团；R2和R3各自独立地选自H、卤素基团、取代或不取代的烃基团、取代或不取代的杂原子基团、取代或不取代的碳环基团、取代或不取代的杂环基团、取代或不取代的芳香基团或取代或不取代的杂芳香基团；R选自H或取代或不取代的烃基团，但R、R2和R3为甲基基团时，R1不是-COCH3。

  公开号：

  WO2011022805A1

文献信息

• [EN] NOVEL COLCHICINE DERIVATIVES, METHODS AND USES THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS DE COLCHICINE, LEURS PROCÉDÉS ET UTILISATIONS
  申请人：ALBERTA HEALTH SERVICES

  公开号：WO2011022805A1

  公开（公告）日：2011-03-03

  The invention relates to colchicine derivatives, methods and uses thereof for treatment of cancer. In certain embodiments, the colchicine derivative comprises a compound of formula (I), wherein Z is O or S; R1 is selected fro H, a halo group, a substituted or unsubstituted hydrocarbon group, or a substituted or unsubstituted heterogeneous group; R2 and R3 are each independently selected from H, a halo group, a substituted or unsubstituted hydrocarbon group, a substituted or unsubstituted heterogeneous group, a substituted or unsubstituted carbocyclic group, a substituted or unsubstituted heterocyclic group, substituted or unsubstituted aromatic, or a substituted or unsubstituted heteroaromatic; R is selected from H or a substituted or unsubstituted hydrocarbon group, with the proviso that when R, R2 and R3 are methyl groups, R1 is not -COCH3.

  本发明涉及秋水仙碱衍生物、其制备方法及其用于治疗癌症的应用。在某些实施例中，秋水仙碱衍生物包括公式(I)的化合物，其中Z是O或S；R1选自H、卤素基团、取代或不取代的烃基团或取代或不取代的杂原子基团；R2和R3各自独立地选自H、卤素基团、取代或不取代的烃基团、取代或不取代的杂原子基团、取代或不取代的碳环基团、取代或不取代的杂环基团、取代或不取代的芳香基团或取代或不取代的杂芳香基团；R选自H或取代或不取代的烃基团，但R、R2和R3为甲基基团时，R1不是-COCH3。
• Tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them
  申请人：Kim Myung-Hwa

  公开号：US20070179143A1

  公开（公告）日：2007-08-02

  The present invention relates to tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. More precisely, the present invention relates to tricyclic derivatives as colchicine derivatives, pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them. Tricyclic derivatives of the present invention show very powerful cytotoxicity to cancer cell lines but were much less toxic than colchicine or taxol, confirmed through animal toxicity test. Tricyclic derivatives of the invention also decrease the volume and weight of a tumor and have a strong angiogenesis inhibiting activity in HUVEC cells. Thus, tricyclic derivatives of the present invention can effectively be used as an anticancer agent, anti-proliferation agent and an angiogenesis inhibitor.

  本发明涉及三环衍生物或其药学上可接受的盐、它们的制备方法以及含有它们的制药组合物。更具体地说，本发明涉及三环衍生物作为秋水仙素衍生物，药学上可接受的盐、它们的制备方法以及含有它们的制药组合物。本发明的三环衍生物对癌细胞株表现出非常强大的细胞毒性，但毒性比秋水仙素或紫杉醇要小得多，经动物毒性测试证实。本发明的三环衍生物还可以减少肿瘤的体积和重量，并在HUVEC细胞中表现出强大的抑制血管生成的活性。因此，本发明的三环衍生物可以有效地用作抗癌剂、抗增殖剂和抑制血管生成剂。
• Method for preparing tricyclic derivatives
  申请人：Kim Myung-Hwa

  公开号：US08742160B2

  公开（公告）日：2014-06-03

  The present invention relates to a method for preparing a tricyclic derivative, and more particularly, to a method for preparing a tricyclic derivative intermediate with high yield and purity, the method including: introducing a hydroxy group by esterifying and substituting 2-fluoroisophthalic acid compound; introducing a piperidyl group; introducing a hydroxy group through reduction reaction; and then hydrolyzing the resultant compound, and to a method for preparing the tricyclic derivative using said intermediate. According to the method of the present invention, it is possible to provide a tricyclic derivative and an intermediate thereof with high productivity and economic feasibility as well as high purity and yield, by purifying a compound using re-crystallization unlike typical methods of using column chromatography. In addition, the method of the present invention can be usefully used for industrial mass production because sodium borohydride or lithium aluminum hydride with low risk of a fire is used unlike typical methods of using lithium borohydride which is not industrially applicable due to high risk of a fire.

  本发明涉及一种制备三环衍生物的方法，更具体地，涉及一种制备高产率和高纯度的三环衍生物中间体的方法，该方法包括：通过酯化和取代2-氟异苯二甲酸化合物引入羟基；引入哌啶基；通过还原反应引入羟基；然后水解所得化合物，并且涉及使用该中间体制备三环衍生物的方法。根据本发明的方法，通过重新结晶纯化化合物而不是使用柱层析等典型方法，可以提供高产率和经济可行性以及高纯度和收率的三环衍生物和中间体。此外，本发明的方法可以用于工业大规模生产，因为使用钠硼氢化物或锂铝氢化物，其火灾风险较低，而不是使用锂硼氢化物这样的典型方法，因为锂硼氢化物由于火灾风险过高而不适用于工业应用。
• Derivatives of thiocolchicine and its applications to CEM cells treatment using 19F Magnetic Resonance ex vivo
  作者：Dorota Bartusik、Boguslaw Tomanek、Erika Lattová、Hélène Perreault、Jack Tuszynski、Gino Fallone

  DOI：10.1016/j.bioorg.2009.10.002

  日期：2010.2

  It was shown, that cultured ex vivo human T-Lymphoblastoid (CEM) cells respond to synthesized thiocolchicine and fluorine thiocolchicine derivatives. The preparation of derivatives with substitution at C-3 and C-7 is described. All compounds were used at concentration from 1 nM to 1000 nM. Inhibitory effects of these compounds were examined in the three-dimensional (3-D) culture and cells morphology during treatment was monitored using 9.4 T MRI system. We performed studies of these compounds in CEM cells ex vivo using H-1 and F-19 Magnetic Resonance Imaging (MRI), F-19 Magnetic Resonance Spectroscopy (MRS), High Performance Liquid Chromatography coupled with Ultra Violet (HPLC-UV) and Electron Impact Mass Spectrometry (EIMS). The results of the multi-technique approach are consistent with the fact that the new derivatives are more efficient than colchicine and thiocolchicine ex vivo. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.
• TRICYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：JE IL Pharmaceutical Co., Ltd.

  公开号：EP1646608B1

  公开（公告）日：2011-03-02