4-Amino-2-hydroxymethyl-5-methoxy-1-methylindole | 318974-76-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-Amino-2-hydroxymethyl-5-methoxy-1-methylindole
• 英文别名: (4-Amino-5-methoxy-1-methyl-1H-indol-2-yl)methanol；(4-amino-5-methoxy-1-methylindol-2-yl)methanol
• CAS: 318974-76-4
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.244
• InChiKey: HMYMRPWLGVWRCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  60.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Amino-2-hydroxymethyl-5-methoxy-1-methylindole 在 potassium nitrososulfonate 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 2-hydroxymethyl-5-methoxy-1-methylindole-4,7-dione
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Indolequinone Phosphoramidate Prodrugs Targeted to DT-diaphorase

  摘要：

  A series of 2- and 3-substituted indolequinone phosphoramidate prodrugs targeted to DT-diaphorase (DTD) have been synthesized and evaluated. These compounds are designed to undergo activation via quinone reduction by DTD followed by expulsion of the phosphoramide mustard substituent from the hydroquinone. Chemical reduction of the phosphoramidate prodrugs led to rapid expulsion of the corresponding phosphoramidate anions in both series of compounds. Compounds substituted at the 2-position are excellent substrates for human DTD (k(cat)/K-M = (2-5) x 10(6) M-1 s(-1)); however, compounds substituted at the 3-position are potent inhibitors of the target enzyme. Both series of compounds are toxic in HT-29 and BE human colon cancer cell lines in a clonogenic assay. There was a correlation found between cytotoxicity and DTD activity for the 2-series of phosphoramidates; however, there was no correlation between cytotoxicity and DTD activity in the 3-series of compounds. This finding suggests the presence of an alternative mechanism for the activation of these compounds.

  DOI：

  10.1021/jm020191b
• 作为产物：
  描述：

  methyl 5-methoxy-1-methyl-1H-indole-2-carboxylate 在 盐酸 、 tin 、 lithium aluminium tetrahydride 、 硝酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 4.25h， 生成 4-Amino-2-hydroxymethyl-5-methoxy-1-methylindole
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Indolequinone Phosphoramidate Prodrugs Targeted to DT-diaphorase

  摘要：

  A series of 2- and 3-substituted indolequinone phosphoramidate prodrugs targeted to DT-diaphorase (DTD) have been synthesized and evaluated. These compounds are designed to undergo activation via quinone reduction by DTD followed by expulsion of the phosphoramide mustard substituent from the hydroquinone. Chemical reduction of the phosphoramidate prodrugs led to rapid expulsion of the corresponding phosphoramidate anions in both series of compounds. Compounds substituted at the 2-position are excellent substrates for human DTD (k(cat)/K-M = (2-5) x 10(6) M-1 s(-1)); however, compounds substituted at the 3-position are potent inhibitors of the target enzyme. Both series of compounds are toxic in HT-29 and BE human colon cancer cell lines in a clonogenic assay. There was a correlation found between cytotoxicity and DTD activity for the 2-series of phosphoramidates; however, there was no correlation between cytotoxicity and DTD activity in the 3-series of compounds. This finding suggests the presence of an alternative mechanism for the activation of these compounds.

  DOI：

  10.1021/jm020191b

文献信息

• Phosphoramide compounds
  申请人：——

  公开号：US20030008850A1

  公开（公告）日：2003-01-09

  The invention provides a compound of formula I: 1 wherein R 1 , R a , R b , R c , and R d have any of the values defined in the specification, as well as pharmaceutical compositions comprising such compounds or salts. The compounds are useful for treating cancer in animals.

  本发明提供了一种I式化合物：1，其中R1、Ra、Rb、Rc和Rd的任何值均定义在规范中，以及包含这种化合物或盐的药物组合物。这些化合物对于治疗动物的癌症具有用处。
• US6656926B2
  申请人：——

  公开号：US6656926B2

  公开（公告）日：2003-12-02
• US7304046B2
  申请人：——

  公开号：US7304046B2

  公开（公告）日：2007-12-04
• Design, Synthesis, and Biological Evaluation of Indolequinone Phosphoramidate Prodrugs Targeted to DT-diaphorase
  作者：Marcy Hernick、Carolee Flader、Richard F. Borch

  DOI：10.1021/jm020191b

  日期：2002.8.1

  A series of 2- and 3-substituted indolequinone phosphoramidate prodrugs targeted to DT-diaphorase (DTD) have been synthesized and evaluated. These compounds are designed to undergo activation via quinone reduction by DTD followed by expulsion of the phosphoramide mustard substituent from the hydroquinone. Chemical reduction of the phosphoramidate prodrugs led to rapid expulsion of the corresponding phosphoramidate anions in both series of compounds. Compounds substituted at the 2-position are excellent substrates for human DTD (k(cat)/K-M = (2-5) x 10(6) M-1 s(-1)); however, compounds substituted at the 3-position are potent inhibitors of the target enzyme. Both series of compounds are toxic in HT-29 and BE human colon cancer cell lines in a clonogenic assay. There was a correlation found between cytotoxicity and DTD activity for the 2-series of phosphoramidates; however, there was no correlation between cytotoxicity and DTD activity in the 3-series of compounds. This finding suggests the presence of an alternative mechanism for the activation of these compounds.