1-((4-fluorophenyl)sulfonyl)-1H-indole | 146384-55-6

• 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: 1-((4-fluorophenyl)sulfonyl)-1H-indole
• 英文别名: 1-(4-fluorobenzenesulfonyl)-indole；1-(4-fluoro-benzenesulfonyl)-1H-indole；1-(4-fluorophenyl)sulfonylindole
• CAS: 146384-55-6
• 化学式: C₁₄H₁₀FNO₂S
• 分子量: 275.303
• InChiKey: BHLXSJMHFZYNKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-((4-fluorophenyl)sulfonyl)-1H-indole 在 正丁基锂 、 溶剂黄146 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 为溶剂， 反应 4.5h， 生成 4-[1-(4-fluoro-benzenesulfonyl)-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
• 作为产物：
  描述：

  吲哚 、 4-氟苯磺酰氯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以89%的产率得到1-((4-fluorophenyl)sulfonyl)-1H-indole
  参考文献：
  名称：

  [EN] THERAPEUTIC COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS THÉRAPEUTIQUES ET LEURS UTILISATIONS

  摘要：

  本发明涉及式(I)的化合物及其盐，其中A具有规范中定义的任何值，以及其组合物和用途。这些化合物可用作CBP和/或EP300的抑制剂。还包括包含式(I)的化合物或其药学上可接受的盐的药物组合物，以及在治疗各种CBP和/或EP300介导的疾病中使用这些化合物和盐的方法。

  公开号：

  WO2016055028A1

文献信息

• [EN] THERAPEUTIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ET LEURS UTILISATIONS
  申请人：GENENTECH INC

  公开号：WO2016055028A1

  公开（公告）日：2016-04-14

  The present invention relates to compounds of formula (I): and to salts thereof, wherein A has any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

  本发明涉及式(I)的化合物及其盐，其中A具有规范中定义的任何值，以及其组合物和用途。这些化合物可用作CBP和/或EP300的抑制剂。还包括包含式(I)的化合物或其药学上可接受的盐的药物组合物，以及在治疗各种CBP和/或EP300介导的疾病中使用这些化合物和盐的方法。
• 4-(1-(sulfonyl)-1h-indol-2-yl)-4-(hydroxy)-cyclohexa-2,5-dienone compounds and analogs thereof as therapeutic agents
  申请人：Stevens Francis Graham Malcolm

  公开号：US20060100265A1

  公开（公告）日：2006-05-11

  This invention pertains to certain 4-(1-(sulfonyl)-1H-indol-2-yl)-4-(hydroxy)-cyclohexa-2,5-dienone compounds, and analogs thereof, including compounds of the following formula, which are, inter alia, antiproliferative agents, anticancer agents, and/or thioredoxin/thioredoxin reductase inhibitors: formula (I) wherein: Ar is a 1-(sulfonyl)-1H-indol-2-yl group; the bond marked α is independently: (a) a single bond; or: (b) a double bond; the bond marked β is independently: (a) a single bond; or: (b) a double bond; the group —OR O is independently: (a) —OH; (b) an ether group (e.g., —OMe); or: (c) an acyloxy (i.e., reverse ester) group (e.g., —OC(═O)Me); each of R 2 , R 3 , R 5 , and R 6 , is independently a ring substituent and is: (a) H; (b) a monovalent monodentate substituent; or: (c) a ring substituent which, together with an adjacent ring substituent, and together with the ring atoms to which these ring substituents are attached, form a fused ring; 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), and/or conditions mediated by thioredoxin/thioredoxin reductase.

  本发明涉及某些4-(1-(磺酰基)-1H-吲哚-2-基)-4-(羟基)-环己-2,5-二酮化合物及其类似物，包括以下式的化合物，它们是抗增殖剂、抗癌剂和/或硫代还蛋白/硫代还蛋白还原酶抑制剂等：式(I)其中：Ar是1-(磺酰基)-1H-吲哚-2-基；标记为α的键独立地是：(a) 单键；或：(b) 双键；标记为β的键独立地是：(a) 单键；或：(b) 双键；—ORO基团独立地是：(a) -OH；(b) 醚基团（例如，-OMe）；或：(c) 酰氧基（即反酯基）基团（例如，-OC（═O）Me）；R2、R3、R5和R6中的每一个独立地是一个环取代基，并且是：(a) H；(b) 单价单齿取代基；或：(c) 与相邻的环取代基一起，并且与这些环取代基附着的环原子一起形成融合环的环取代基；以及其药学上可接受的盐、酯、酰胺、溶剂化物、水合物和保护形式。本发明还涉及包含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）和/或由硫代还蛋白/硫代还蛋白还原酶介导的疾病中。
• Copper-catalyzed construction of (<i>Z</i>)-benzo[<i>cd</i>]indoles: stereoselective intramolecular <i>trans</i>-addition and S_N–Ar reaction
  作者：Xinyue Wang、Heyang Zeng、Wenli Zhang、Haiyang Guo、Tao Jin、Senlei Shi、Xiaoyuan Jin、Na Qu、Li Liu、Lianpeng Zhang

  DOI：10.1039/d2ob01488b

  日期：——

  copper-catalyzed one-step synthesis of biologically important polysubstituted benzo[cd]indoles starting from 8-alkynyl-1-naphthylamine derivatives is reported. In this protocol, many substituents tolerated the reaction conditions and produced (Z)-benzo[cd]indoles in good yields. Preliminary mechanistic studies indicated that the reaction proceeds via a stereoselective intramolecular trans-addition and SN–Ar

  取代的苯并[ cd ]吲哚是最有吸引力的框架之一，因为它们具有广泛的生物和光学活性。本文报道了一种以 8-alkynyl-1-naphthylamine 衍生物为原料的铜催化一步合成生物学上重要的多取代苯并[ cd ]吲哚。在该方案中，许多取代基能够耐受反应条件并以良好的产率产生 ( Z )-苯并[ cd ]吲哚。初步机理研究表明，该反应通过立体选择性分子内反式加成和 S N -Ar 反应进行，具有高选择性和高收率。合成的多取代（Z)-苯并[ cd ]吲哚具有磺酰胺结构单元，这使它们成为生物活性分子的候选者。
• Therapeutic compounds and uses thereof
  申请人：GENENTECH, INC.

  公开号：US10206931B2

  公开（公告）日：2019-02-19

  The present invention relates to compounds of formula (I): and to salts thereof, wherein A has any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

  本发明涉及式（I）化合物： 及其盐，其中 A 具有说明书中定义的任一值，以及其组合物和用途。这些化合物可用作 CBP 和/或 EP300 的抑制剂。还包括包含式（I）化合物或其药学上可接受的盐的药物组合物，以及使用此类化合物和盐治疗各种CBP和/或EP300介导的疾病的方法。
• 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