(7S,9S)-9-acetyl-7-<(3'-amino-2',3',6'-trideoxy-α-L-arabinohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5,12-naphthacenedione | 62414-03-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: (7S,9S)-9-acetyl-7-<(3'-amino-2',3',6'-trideoxy-α-L-arabinohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5,12-naphthacenedione
• 英文别名: (7S,9S)-9-acetyl-7-[(3'-amino-2',3',6'-trideoxy-α-L-arabinohexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5,12-naphthacenedione；(7S,9S)-9-acetyl-7-[(2R,4S,5R,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-8,10-dihydro-7H-tetracene-5,12-dione
• CAS: 62414-03-3
• 化学式: C₂₆H₂₇NO₉
• 分子量: 497.502
• InChiKey: XDXDZDZNSLXDNA-UKTGYDETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  177
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (7S,9S)9-乙酰基-7,8,9,10-四氢-6,7,9,11-四羟基-5,12-并四苯二酮 在 sodium hydroxide 、 silver trifluoromethanesulfonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 (7S,9S)-9-acetyl-7-<(3'-amino-2',3',6'-trideoxy-α-L-arabinohexopyranosyl)oxy>-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5,12-naphthacenedione
  参考文献：
  名称：

  Synthesis and antitumor activity of novel 4-demethoxyanthracyclines

  摘要：

  A versatile and efficient synthetic route to 4-demethoxyanthracyclinones has been utilized in the preparation of a number of aglycons having 9-alkyl, 9-(hydroxylalkyl), or 9-carbamoyl substituents. Silver trifluoromethanesulfonate catalyzed coupling of these aglycons with various daunosamine derivatives has yielded a series of novel anthracyclines which have been evaluated as antitumor agents. 9-Alkylanthracyclines 22, 23, 33, and 34 have higher efficacy vs L-1210 leukemia than the parent 4-demethoxydaunorubicin (21), or the natural anthracyclines daunorubicin (1) and doxorubicin (2). 9-(Hydroxyalkyl) derivatives have in most cases high efficacy but are slightly less potent than 21. 9-Methyl analogue 22 has higher efficacy vs P388 leukemia than other anthracyclines tested, while 9-(hydroxymethyl) derivative 37 retains similar efficacy to anthracyclines 1, 2, and 21 but is considerably more potent. The N-substituted 9-carbamoylanthracyclines are devoid of antitumor activity.

  DOI：

  10.1021/jm00171a010

文献信息

• Methods and Compositions for Treating or Preventing Cancer
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20150093398A1

  公开（公告）日：2015-04-02

  This invention relates to compositions and methods useful for treating various cancers. Therapeutic combinations and methods of use thereof are also covered in the present application.

  本发明涉及用于治疗各种癌症的组合物和方法。本申请还涵盖了治疗组合物和使用方法。
• USE OF TRANS-[TETRACHLOROBIS(1H-INDAZOLE)RUTHENATE(III)] FOR THE TREATMENT OF CANCER
  申请人：Bold Therapeutics, Inc.

  公开号：US20210085647A1

  公开（公告）日：2021-03-25

  IT-139, sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)], is an intravenously administered small molecule compound. In preclinical anti-tumor and mechanism of action studies, IT-139 showed activity against a broad range of tumor types, including those which are resistant to standard anti-cancer agents (e.g., platinums, vinca alkaloids, taxanes, anthracyclines). This activity is believed to arise from IT-139's novel mechanism of action that targets the GRP78 pathway. It was found that up-regulation of GRP78 is a key cancer cell survival pathway. Downregulation of GRP78 using IT-139 removes this resistance pathway allowing for chemotherapy and immuno-oncology agents to be more effective in treating cancer.
• Synthesis and antitumor activity of novel 4-demethoxyanthracyclines
  作者：Nigel Adams、Colin Blake、Michael J. Broadhurst、David J. Bushnell、Cedric H. Hassall、Hans R. Hartmann、Elizabeth Keech、Alan R. Stratton、Gareth J. Thomas

  DOI：10.1021/jm00171a010

  日期：1990.9

  A versatile and efficient synthetic route to 4-demethoxyanthracyclinones has been utilized in the preparation of a number of aglycons having 9-alkyl, 9-(hydroxylalkyl), or 9-carbamoyl substituents. Silver trifluoromethanesulfonate catalyzed coupling of these aglycons with various daunosamine derivatives has yielded a series of novel anthracyclines which have been evaluated as antitumor agents. 9-Alkylanthracyclines 22, 23, 33, and 34 have higher efficacy vs L-1210 leukemia than the parent 4-demethoxydaunorubicin (21), or the natural anthracyclines daunorubicin (1) and doxorubicin (2). 9-(Hydroxyalkyl) derivatives have in most cases high efficacy but are slightly less potent than 21. 9-Methyl analogue 22 has higher efficacy vs P388 leukemia than other anthracyclines tested, while 9-(hydroxymethyl) derivative 37 retains similar efficacy to anthracyclines 1, 2, and 21 but is considerably more potent. The N-substituted 9-carbamoylanthracyclines are devoid of antitumor activity.