N-脱乙酰基3-去甲基硫代秋水仙碱 | 97043-09-9

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 中文名称: N-脱乙酰基3-去甲基硫代秋水仙碱
• 英文名称: N-[(7S)-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]amine
• 英文别名: 3-demethyldeacetylthiocolchicine；(S)-7-amino-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]heptalen-9-one；(S)-7-Amino-3-hydroxy-1,2-dimethoxy-10-methylmercapto-6,7-dihydro-5H-benzo[a]heptalen-9-on；N-Desacetyl 3-Demethyl Thiocolchicine；(7S)-7-amino-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-6,7-dihydro-5H-benzo[a]heptalen-9-one
• CAS: 97043-09-9
• 化学式: C₁₉H₂₁NO₄S
• 分子量: 359.446
• InChiKey: YSTRXCPUTQBTQG-ZDUSSCGKSA-N

物化性质

• 熔点：
  >175°C (dec.)
• 溶解度：
  乙腈（轻微溶解，超声处理），氯仿（轻微溶解，加热，超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  3-去甲基硫代秋水仙碱	3-O-demethylthiocolchicine	87424-25-7	C21H23NO5S	401.483
  硫代秋水仙碱	thiocolchicine	2730-71-4	C22H25NO5S	415.51
  秋水仙碱	colchicine	64-86-8	C22H25NO6	399.444
  硫秋水仙苷	thiocolchicoside	602-41-5	C27H33NO10S	563.626

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	3-demethylthiodemecolcine	123643-49-2	C20H23NO4S	373.473
  ——	N-formyl-3-demethyldeacetylthiocolchicine	113092-25-4	C20H21NO5S	387.456
  ——	methyl N-[(7S)-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]carbamate	911303-83-8	C21H23NO6S	417.483
  ——	N-butyryl-3-demethyldeacetylthiocolchicine	123643-58-3	C23H27NO5S	429.537
  ——	N-(ethoxycarbonyl)-3-demethyldeacetylthiocolchicine	97043-06-6	C22H25NO6S	431.51
  ——	N-(trifluoroacetyl)-3-demethyldeacetylthiocolchicine	123643-51-6	C21H20F3NO5S	455.455
  ——	N-[(7S)-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]-N-[(trifluoroacetyl)glycyl]amine	1208314-86-6	C23H23F3N2O6S	512.507
  ——	N-(trifluoroacetyl)-3-demethylthiodemecolcine	123643-52-7	C22H22F3NO5S	469.482
  ——	N,O-dibutyryl-3-demethyldeacetylthiocolchicine	123643-57-2	C27H33NO6S	499.628

反应信息

• 作为反应物：
  描述：

  N-脱乙酰基3-去甲基硫代秋水仙碱 在 咪唑 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.67h， 生成 methyl N-[(7S)-3-hydroxy-1,2-dimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]carbamate
  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
• 作为产物：
  描述：

  秋水仙碱 在 盐酸 、 水 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-脱乙酰基3-去甲基硫代秋水仙碱
  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

• 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.
• WO2020000109A5
  申请人：——

  公开号：WO2020000109A5

  公开（公告）日：2022-06-22
• Synthesis and biological effects of novel thiocolchicines. 3. evaluation of N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, and O-ethyldemethylthiocolchicines. New synthesis of thiodemecolcine and antileukemic effects of 2-demethyl- and 3-demethylthiocolchicine
  作者：Peter Kerkes、Padam N. Sharma、Arnold Brossi、Colin F. Chignell、Frank R. Quinn

  DOI：10.1021/jm00147a014

  日期：1985.9

  Novel and known analogues of thiocolchicine were evaluated in vitro in a tubulin binding assay and in vivo in mice for acute toxicity and in the P388 lymphocytic leukemia assay. This evaluation included N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, thiodemecolcine and its methyl carbamate, and O-ethyl ethers of demethylthiocolchicines. Selective ether cleavage of thiodemecolcine with concentrated sulfuric acid at 50 degree C afforded the 2-demethyl congener, characterized as its N,O-diacetyl derivative. Several of the compounds showed high potency in the tubulin binding assay, matching the potency of colchicine. Several N-(alkoxycarbonyl)deacetylcolchicines (carbamates) exhibited strong binding affinity to tubulin but had only weak activities against the P388 tumor system, suggesting that other factors besides tubulin binding may be important for the biological effects. The compounds potent in the tubulin binding assay and in the P388 leukemia assay in mice were generally also toxic to mice in the acute toxicity test, showing thus a similar behavior of thiocolchicines to that observed earlier with colchicines. A considerable amount of data collected for 2-demethyl- and 3-demethylthiocolchicine suggests that the latter represents a broad-spectrum antitumor agent of considerable promise and possibly a less toxic substitute for colchicine.
• Antitubulin effects of derivatives of 3-demethylthiocolchicine, methylthio ethers of natural colchicinoids, and thioketones derived from thiocolchicine. Comparison with colchicinoids
  作者：Anjum Muzaffar、Arnold Brossi、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00164a015

  日期：1990.2

  Esterification of the phenolic group in 3-demethylthiocolchicine and exchange of the N-acetyl group with other N-acyl groups or a N-carbalkoxy group afforded many compounds which showed superior activity over the parent drug as inhibitors of tubulin polymerization and of the growth of L1210 murine leukemia cells in culture. A comparison of naturally occurring Colchicum alkaloids with thio isosters, obtained by replacing the OMe group at C(10) with a SCH3 group, showed the thio ethers to be invariably more potent in these assays. The comparison included 3-demethylthiodemecolcine prepared from 3-demethylthiocolchicine by partial synthesis. Thiation of thiocolchicine with Lawesson's reagent afforded novel thiotropolones which exhibited high antitubulin activity. Their structures are fully secured by spectral data. Colchicine and several of its analogues show good antitumor effect in mice infected with P388 lymphocytic leukemia, and all of them show high affinity for tubulin and inhibit tubulin polymerization at low concentration. Consequently, antitubulin assays with this class of compounds can serve as valuable prescreens for the initial evaluation of potential antitumor drugs.
• Velluz; Muller, Bulletin de la Societe Chimique de France, 1955, p. 198
  作者：Velluz、Muller

  DOI：——

  日期：——