4-hydroxy-4-(1H-indol-2-yl)cyclohexa-2,5-dien-1-one

• 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-hydroxy-4-(1H-indol-2-yl)cyclohexa-2,5-dien-1-one
• 化学式: C₁₄H₁₁NO₂
• 分子量: 225.247
• InChiKey: LUFNDEABXKJGRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N,N-二甲基-1H-吲哚-1-甲胺 在 sodium tetrahydroborate 、 正丁基锂 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 6.83h， 生成 4-hydroxy-4-(1H-indol-2-yl)cyclohexa-2,5-dien-1-one
  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-Aryl quinols and analogs thereof as therapeutic agents
  申请人：——

  公开号：US20040220236A1

  公开（公告）日：2004-11-04

  The present invention pertains to compounds of the formula (I) which are, inter alia, antiprolilferative agents, anticancer agents, anitimycohacterial agents, antituberculosis agents, and/or thioredoxin/thioredoxin reductase inhibitor: wherein: Q is ═O or ═N—S(═O) 2 —R Q ; R Q is -II or optionally substituted C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl; Ar is optionally substituted C 5-20 aryl; R O is an oxy substituent; the bond marked &agr; is a single bond or a double bond; the bond marked &bgr; is a single bond or a double bond; R 3 and R 5 are each independently ring substituents; R 2 and R 6 are each independently ring substituents; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for example, in the treatment of proliferative conditions, (e.g., cancer), mycobacterial infections (e.g., tuberculosis), and/or conditions mediated by thioredoxin/thioredoxin reductase. 1

  本发明涉及化合物的公式（I），其是抗增殖剂，抗癌剂，抗结核菌剂，抗结核病剂和/或硫氧还蛋白/硫氧还蛋白还原酶抑制剂，其中：Q是═O或═N-S（═O）2-RQ; RQ是-II或可选取代的C1-7烷基，C3-20杂环基或C5-20芳基; Ar是可选取代的C5-20芳基; RO是氧代取代基; 标记为&agr;的键是单键或双键; 标记为&bgr;的键是单键或双键; R3和R5各自独立地是环取代基; R2和R6各自独立地是环取代基; 以及其药学上可接受的盐，酯，酰胺，溶剂化合物，水合物和保护形式。本发明还涉及包含这种化合物的制药组合物，以及这种化合物和组合物的使用，无论是体外还是体内，例如，用于治疗增殖性疾病（例如癌症），结核菌感染（例如结核病）和/或由硫氧还蛋白/硫氧还蛋白还原酶介导的疾病。
• 4-aryl quinols and analogs thereof as therapeutic agents
  申请人：Stevens Francis Graham Malcolm

  公开号：US20060287396A1

  公开（公告）日：2006-12-21

  The present invention pertains to compounds of the following formula, which are, inter alia, antiproliferative agents, anticancer agents, antimycobacterial agents, antituberculosis agents, and/or thioredoxin/thioredoxin reductase inhibitors: wherein: Q is ═O or ═N—S(═O) 2 —R Q ; R Q is —H or optionally substituted C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl; Ar is optionally substituted C 5-20 aryl; R O is an oxy substituent; the bond marked α is a single bond or a double bond; the bond marked β is a single bond or a double bond; R 3 and R 5 are each independently ring substituents; R 2 and R 6 are each independently ring substituents; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for example, in the treatment of proliferative conditions, (e.g., cancer), mycobacterial infections (e.g., tuberculosis), and/or conditions mediated by thioredoxin/thioredoxin reductase.

  本发明涉及以下式的化合物，它们是抗增殖剂、抗癌剂、抗分枝杆菌剂、抗结核菌剂和/或硫氧还蛋白/硫氧还蛋白还原酶抑制剂，其中：Q为═O或═N—S(═O)2—RQ；RQ为—H或可选取代的C1-7烷基、C3-20杂环基或C5-20芳基；Ar为可选取代的C5-20芳基；RO为氧代取代基；标记为α的键为单键或双键；标记为β的键为单键或双键；R3和R5各自独立地为环取代基；R2和R6各自独立地为环取代基；以及其药学上可接受的盐、酯、酰胺、溶剂化合物、水合物和保护形式。本发明还涉及包括这样的化合物的制药组合物，以及这样的化合物和组合物的使用，无论是体外还是体内，例如在治疗增殖性疾病（例如癌症）、分枝杆菌感染（例如结核病）和/或由硫氧还蛋白/硫氧还蛋白还原酶介导的疾病中。
• 4-ARYL QUINOLS AND ANALOGS THEREOF AS THERAPEUTIC AGENTS
  申请人：Cancer Research Technology Limited

  公开号：EP1404659A1

  公开（公告）日：2004-04-07
• 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
• US7144893B2
  申请人：——

  公开号：US7144893B2

  公开（公告）日：2006-12-05