4,4-Dimethoxy-1-(1-naphthalen-2-ylsulfonylindol-2-yl)cyclohexa-2,5-dien-1-ol | 1026801-82-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4,4-Dimethoxy-1-(1-naphthalen-2-ylsulfonylindol-2-yl)cyclohexa-2,5-dien-1-ol
• CAS: 1026801-82-0
• 化学式: C₂₆H₂₃NO₅S
• 分子量: 461.538
• InChiKey: KLQNDEJXWANSDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  86.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4,4-Dimethoxy-1-(1-naphthalen-2-ylsulfonylindol-2-yl)cyclohexa-2,5-dien-1-ol 在 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 4-hydroxy-4-[1-(naphthalene-2-sulfonyl)-1H-indol-2-yl]-cyclohexa-2,5-dienone
  参考文献：
  名称：

  Quinols as Novel Therapeutic Agents. 2. 4-(1-Arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-ones and Related Agents as Potent and Selective Antitumor Agents

  摘要：

  A series of substituted 4-(1-arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2, 5-dien-1-ones (indolylquinols) has been synthesized on the basis of the discovery of lead compound la and screened for antitumor activity. Synthesis of this novel series was accomplished via the one-pot" addition of lithiated (arylsulfonyl)indoles to 4,4-dimethoxycyclohexa-2,5-dienone followed by deprotection under acidic conditions. Similar methodology gave rise to the related naphtho-, 1H-indole-, and benzimidazole-substituted quinols. A number of compounds in this new series were found to possess in vitro human tumor cell line activity substantially more potent than the recently reported antitumor 4-substituted 4-hydroxycyclohexa-2,5-dien-1-ones(1) with similar patterns of selectivity against colon, renal, and breast cell lines. The most potent compound in the series in vitro, 4-(1-benzenesulfonyl-6-fluoro-1H-indol-2-yl)-4-hydroxycyclohexa-2,5-dienone (1h), exhibits a mean GI(50) value of 16 nM and a mean LC50 value of 2.24 muM in the NCl 60cell-line screen, with LC50 activity in the HCT 116 human colon cancer cell line below 10 nM. The crystal structure of the unsubstituted indolylquinol la exhibits two independent, molecules. both participating in intermolecular hydrogen bonds from quinol OH to carbonyl O-2 but one OH group also interacts intramolecularly with a sulfonyl O atom. This interaction, which strengthens upon ab initio optimization, may influence the chemical environment. of the bioactive quinol moiety. In vivo, significant antitumor activity was recorded (day 28) in mice bearing subcutaneously implanted MDA-MB-435 xenografts, following intraperitoneal treatment of mice with compound 1a at 50 mg/kg.

  DOI：

  10.1021/jm040859h
• 作为产物：
  描述：

  吲哚 在 sodium hydroxide 、 正丁基锂 、 四丁基硫酸氢铵 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 19.5h， 生成 4,4-Dimethoxy-1-(1-naphthalen-2-ylsulfonylindol-2-yl)cyclohexa-2,5-dien-1-ol
  参考文献：
  名称：

  Quinols as Novel Therapeutic Agents. 2. 4-(1-Arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-ones and Related Agents as Potent and Selective Antitumor Agents

  摘要：

  A series of substituted 4-(1-arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2, 5-dien-1-ones (indolylquinols) has been synthesized on the basis of the discovery of lead compound la and screened for antitumor activity. Synthesis of this novel series was accomplished via the one-pot" addition of lithiated (arylsulfonyl)indoles to 4,4-dimethoxycyclohexa-2,5-dienone followed by deprotection under acidic conditions. Similar methodology gave rise to the related naphtho-, 1H-indole-, and benzimidazole-substituted quinols. A number of compounds in this new series were found to possess in vitro human tumor cell line activity substantially more potent than the recently reported antitumor 4-substituted 4-hydroxycyclohexa-2,5-dien-1-ones(1) with similar patterns of selectivity against colon, renal, and breast cell lines. The most potent compound in the series in vitro, 4-(1-benzenesulfonyl-6-fluoro-1H-indol-2-yl)-4-hydroxycyclohexa-2,5-dienone (1h), exhibits a mean GI(50) value of 16 nM and a mean LC50 value of 2.24 muM in the NCl 60cell-line screen, with LC50 activity in the HCT 116 human colon cancer cell line below 10 nM. The crystal structure of the unsubstituted indolylquinol la exhibits two independent, molecules. both participating in intermolecular hydrogen bonds from quinol OH to carbonyl O-2 but one OH group also interacts intramolecularly with a sulfonyl O atom. This interaction, which strengthens upon ab initio optimization, may influence the chemical environment. of the bioactive quinol moiety. In vivo, significant antitumor activity was recorded (day 28) in mice bearing subcutaneously implanted MDA-MB-435 xenografts, following intraperitoneal treatment of mice with compound 1a at 50 mg/kg.

  DOI：

  10.1021/jm040859h