4-[1-(2,4,6-triisopropyl-benzene-4-sulfonyl)-1H-indol-2-yl]-4-hydroxy-cyclohexa-2,5-dienone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[1-(2,4,6-triisopropyl-benzene-4-sulfonyl)-1H-indol-2-yl]-4-hydroxy-cyclohexa-2,5-dienone
• 英文别名: 4-Hydroxy-4-[1-[2,4,6-tri(propan-2-yl)phenyl]sulfonylindol-2-yl]cyclohexa-2,5-dien-1-one
• 化学式: C₂₉H₃₃NO₄S
• 分子量: 491.651
• InChiKey: AHYUVLVIKDTEAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  84.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,4-Dimethoxy-1-[1-[2,4,6-tri(propan-2-yl)phenyl]sulfonylindol-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-[1-(2,4,6-triisopropyl-benzene-4-sulfonyl)-1H-indol-2-yl]-4-hydroxy-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

文献信息

• 4- 1- (SULFONYL) -1H-INDOL-2-YL)-4- (HYDROXY) -CYCLOHEXA-2,5-DIENONE COMPOUNDS AND ANALOGS THEREOF AS THERAPEUTIC AGENTS
  申请人：Cancer Research Technology Limited

  公开号：EP1572197B1

  公开（公告）日：2009-07-29
• US7307099B2
  申请人：——

  公开号：US7307099B2

  公开（公告）日：2007-12-11
• 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
  作者：Jane M. Berry、Tracey D. Bradshaw、Iduna Fichtner、Ruobo Ren、Carl H. Schwalbe、Geoffrey Wells、Eng-Hui Chew、Malcolm F. G. Stevens、Andrew D. Westwell

  DOI：10.1021/jm040859h

  日期：2005.1.1

  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.