2-(5-bromo-1H-indol-2-yl)phenol | 360791-66-8

• 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: 2-(5-bromo-1H-indol-2-yl)phenol
• CAS: 360791-66-8
• 化学式: C₁₄H₁₀BrNO
• 分子量: 288.143
• InChiKey: SRPGWYZXMBNJMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(5-bromo-1H-indol-2-yl)phenol 在 喹啉 、 羟胺 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 N-Hydroxy-2-(2-hydroxy-phenyl)-1H-indole-5-carboxamidine
  参考文献：
  名称：

  Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa

  摘要：

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

  DOI：

  10.1021/jm0100638
• 作为产物：
  描述：

  2-(1-(2-(4-溴苯基)亚肼基)乙基)苯酚 在 PPA 作用下， 反应 3.0h， 生成 2-(5-bromo-1H-indol-2-yl)phenol
  参考文献：
  名称：

  Derivatives of 5-amidine indole as inhibitors of thrombin catalytic activity

  摘要：

  Substituted 5-amidine indoles were constructed based upon a computational analysis of putative modes of binding to thrombin utilizing coordinates from the crystal structure of BMS-183,507-alpha-thrombin complex. These analogs display competitive kinetics for the inhibition of human cr-thrombin. The most potent member of this series 17, shows marked potency for thrombin with an inhibition constant, K-i of 260 nM. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00229-6

文献信息

• Transition-metal-free synthesis of indole-fused dibenzo[b,f][1,4]oxazepines via Smiles rearrangement
  作者：Fangdong Hu、Huanhuan Liu、Jiong Jia、Chen Ma

  DOI：10.1039/c6ob02098d

  日期：——

  transition-metal-free approach for the synthesis of indole-fused dibenzo[b,f][1,4]oxazepines from 2-(1H-indol-2-yl)phenol and 1,2-dihalobenzenes or 2 halonitroarenes has been developed. The proposed mechanism for this transformation features a Smiles rearrangement favoured over a direct intramolecular nucleophilic cyclization, which affords the corresponding products in different regioselectivities

  对于吲哚稠合二苯并[合成的单釜过渡金属无方法b，˚F ] [1,4]由2-（1-氧氮杂ħ吲哚-2-基）苯酚和1,2-二卤代苯或已经开发了2种卤代硝基芳烃。所提出的这种转化机制的特征是，微笑分子重排优于直接分子内亲核环化，后者可提供具有不同区域选择性的相应产物。该反应还具有简单的反应条件和宽泛的官能团耐受性。
• One-Pot Highly Regioselective Synthesis of Indole-Fused Pyridazino[4,5-b][1,4]benzoxazepin-4(3H)-ones by a Smiles Rearrangement
  作者：Xiaolei Jiang、Fangdong Hu

  DOI：10.1055/s-0037-1609338

  日期：2018.6

  A simple and convenient synthesis of indole-fused pyridazino[4,5-b][1,4]benzoxazepin-4(3H)-ones is described. A range of 2-(1H-indol-2-yl)phenols and 4,5-dichloropyridazin-3-ones are compatible with this reaction. A Smiles rearrangement is proposed as a key step in the highly regioselective construction of the products. The easy availability of the starting materials makes this an appealing method

  介绍了一种简单方便的吲哚稠合哒嗪 [4,5-b][1,4] benzoxazep​​in-4(3H)-ones 的合成方法。一系列 2-(1H-indol-2-yl)phenols 和 4,5-dichloropyridazin-3-ones 与该反应相容。Smiles 重排被认为是产品高度区域选择性构建的关键步骤。起始材料的易得性使其成为有机合成中的一种有吸引力的方法。
• A Convenient Synthesis of Fluoroalkylated Benzimidazole‐ or Indole‐fused Benzoxazines
  作者：Yijie Hu、Xiaoli Wang、Nan Ren、Na Li、Jianyang Li、Jie Chen、Hui Zhang、Hongmei Deng、Weiguo Cao、Jin‐Hong Lin

  DOI：10.1002/ejoc.202101501

  日期：2022.2.4

  Described herein is the first synthesis of fluoroalkylated benzimidazole- or indole-fused benzoxazines by using fluoroalkylated propiolates as building blocks. The benzimidazole-fused products were obtained by a convenient one-pot two-step process, a feature that may make this protocol attractive. The incorporation of a fluoroalkyl group into these heterocycles may provide more opportunities for drug

  本文描述了通过使用氟烷基化丙炔酸酯作为结构单元来合成氟烷基化苯并咪唑或吲哚稠合的苯并恶嗪。苯并咪唑融合产品是通过方便的一锅两步工艺获得的，这一特性可能使该协议具有吸引力。将氟烷基结合到这些杂环中可能会为药物开发提供更多机会。
• Palladium-catalyzed annulative allylic alkylation for regioselective construction of indole-fused medium-sized cyclic ethers
  作者：Ling-Qi Chen、Chi-Fan Zhu、Su Zhang、Bao-Yang Liu、Shu-Jiang Tu、Wen-Juan Hao、Bo Jiang

  DOI：10.1016/j.cclet.2023.108398

  日期：2023.3

  A new palladium-catalyzed annulative allylic alkylation (AAA) reaction of 2-(indol-2-yl)phenols with dual allylic electrophiles such as isobutylene dicarbonate and butene dicarbonate is described, leading to the regioselective synthesis of tetracyclic medium-sized cyclic ethers possessing a bridged aryl-indole scaffold, namely, benzo[2,3]oxocino[4,5-b]indoles and benzo[2,3]oxepino[4,5-b]indoles, in

  描述了一种新的钯催化的2-(吲哚-2-基)苯酚与二碳酸异丁烯和二碳酸丁烯等双烯丙基亲电子试剂的环烯丙基烷基化 (AAA) 反应，导致四环中等尺寸环醚的区域选择性合成桥联芳基吲哚支架，即苯并[2,3]氧辛基[4,5- b ]吲哚和苯并[2,3]氧吡啶[4,5- b ]吲哚，产率良好至优异。该方案展示了广泛的底物范围、与取代基的良好兼容性和高区域选择性，为创建桥联芳基吲哚骨架提供了一种催化和灵活的方法。
• US4220356A
  申请人：——

  公开号：US4220356A

  公开（公告）日：1980-09-02