2-(6-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride | 3828-10-2

• 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-(6-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride
• CAS: 3828-10-2
• 化学式: C₁₀H₅ClFNO₂
• 分子量: 225.607
• InChiKey: HRDNIVYOZFIBFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(6-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride 在 lithium aluminium tetrahydride 、 氨 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 6-氟色氨酸
  参考文献：
  名称：

  Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties

  摘要：

  A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl) amino]methyl}furan-2-yl)phenol (1, 5-HT6R K-i = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R K-j= 25, 5-HT2AR K-i = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with procognitive properties. (C) 2019 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111857
• 作为产物：
  描述：

  6-氟-1H-吲哚-2-羧酸甲酯 在 N-甲基吡咯烷酮 、 sodium hydroxide 、 铜 作用下， 以 乙醚 为溶剂， 反应 11.0h， 生成 2-(6-fluoro-1H-indol-3-yl)-2-oxoacetyl chloride
  参考文献：
  名称：

  Effect of Ring Fluorination on the Pharmacology of Hallucinogenic Tryptamines

  摘要：

  A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activation of these compounds at serotonin receptor subtypes. The target compounds were evaluated using in vivo behavioral assays for hallucinogen-like and 6-HT1A agonist activity and in vitro radioligand competition assays for their affinity at 5-HT2A, 5-HT2C, and 5-HT1A receptor sites. Functional activity at the 5-HT2A receptor was determined for all compounds. In addition, for some compounds functional activity was determined at the 5-HT1A receptor. Hallucinogen-like activity, evaluated in the two-lever drug discrimination paradigm using LSD-trained rats, was attenuated or abolished for all of the fluorinated analogues. One of the tryptamines, 4-fluoro-5-methoxy-DMT (6), displayed high 5-HT1A agonist activity, with potency greater than that of the 5-HT1A agonist 8-OH-DPAT. The ED50 Of 6 in the two-lever drug discrimination paradigm using rats trained to discriminate the 5-HT1A agonist LY293284 was 0.17 mu mol/kg, and the K-i at [H-3] 8-OH-DPAT-labeled 5-HT1A receptors was 0.23 nM. The results indicate that fluorination of hallucinogenic tryptamines generally has little effect on 5-HT2A/2C receptor affinity or intrinsic activity. Affinity at the 5-HT1A receptor was reduced, however, in all but one example, and all of the compounds tested were full agonists but with reduced functional potency at this serotonin receptor subtype. The one notable exception was 4-fluoro-5-methoxy-DMT (6), which had markedly enhanced 5-HT1A receptor affinity and functional potency. Although it is generally considered that hallucinogenic activity results from 5-HT2A receptor activation, the present results suggest a possible role for involvement of the 5-HT1A receptor with tryptamines.

  DOI：

  10.1021/jm000339w

文献信息

• Design, synthesis, and evaluation of novel anti-trypanosomal compounds
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  DOI：10.1016/j.tet.2020.131086

  日期：2020.4

  screening a collection of diverse nitrogenous heterocycles, we discovered two novel compounds that contain the tetracyclic core of the Yohimbine and Corynanthe alkaloids, were potent inhibitors of T. brucei proliferation and T. brucei methionyl-tRNA synthetase (TbMetRS) activity. Inspired by these key findings, we prepared several novel series of hydroxyalkyl δ-lactam, δ-lactam, and piperidine analogs and

  人类非洲锥虫病 (HAT) 是一种致命的被忽视的热带疾病，由原生动物寄生虫布氏锥虫引起。在筛选一系列不同的含氮杂环化合物的过程中，我们发现了两种新化合物，它们含有育亨宾和 Corynanthe 生物碱的四环核心，它们是布氏杆菌增殖和布氏杆菌甲硫氨酰-tRNA 合成酶 (TbMetRS) 活性的有效抑制剂。受这些关键发现的启发，我们制备了几个新系列的羟烷基 δ-内酰胺、δ-内酰胺和哌啶类似物，并测试了它们的抗锥虫活性。许多抑制剂对布氏锥虫的作用比这些最初的抑制剂更有效，其中一种羟烷基 δ-内酰胺衍生物在我们的测定中有效 25 倍。令人惊讶的是，这些活性化合物中的大多数都未能抑制 TbMetRS。
• Design, Synthesis and Cytotoxicity of Novel Podophyllotoxin Derivatives
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  DOI：10.1248/cpb.56.831

  日期：——

  A series of novel podophyllotoxin derivatives were designed using association strategy and synthesized by coupling either podophyllotoxin (1) or 4beta-amino podophyllotoxin (3) with substituted indol-3-yl-glyoxyl chlorides. Their structures were identified using spectroscopic techniques. These novel derivatives have been evaluated for cytotoxicity in vitro against four human cancer cell lines with

  使用缔合策略设计了一系列新颖的鬼臼毒素衍生物，并通过将鬼臼毒素（1）或4β-氨基鬼臼毒素（3）与取代的吲哚-3-基-乙二酰氯偶联而合成。使用光谱技术鉴定了它们的结构。与母体化合物1、3和靛蓝蛋白（2）相比，已经评估了这些新型衍生物在体外对四种人类癌细胞系的细胞毒性。一些化合物（7a，7c）显示出与鬼臼毒素相当的细胞毒性。
• Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities
  作者：Mukund P. Tantak、Vishakha Gupta、Kumar Nikhil、V. Arun、Rajnish Prakash Singh、Prabhat Nath Jha、Kavita Shah、Dalip Kumar

  DOI：10.1016/j.bmcl.2016.04.080

  日期：2016.7

  bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds 10d, 10g and 10i were found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a-n were evaluated against a panel of human cancer cell lines. Of the screened analogues

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• Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade
  作者：Long Han、Chuan Liu、Wei Zhang、Xiao-Xin Shi、Shu-Li You

  DOI：10.1039/c3cc47921h

  日期：——

  An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.

  通过衍生自C2对称双异羟肟酸（BHA）配体的手性钒催化剂实现了对三酚的对映选择性环氧化，然后进行了分子内环氧化物开环反应。在温和的反应条件下获得了产率高达89％和ee达90％的3a-羟基呋喃二氢吲哚衍生物。
• 3-(7-Azaindolyl)-4-indolylmaleimides as a novel class of mutant isocitrate dehydrogenase-1 inhibitors: Design, synthesis, and biological evaluation
  作者：Yuanyuan Hu、Anhui Gao、Honghui Liao、Mengmeng Zhang、Gaoya Xu、Lixin Gao、Lei Xu、Yubo Zhou、Jianrong Gao、Qing Ye、Jia Li

  DOI：10.1002/ardp.201800039

  日期：2018.10

  A series of 3‐(7‐azainodyl)‐4‐indolylmaleimides was designed, synthesized, and evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory activities. Many compounds such as 11a, 11c, 11e, 11g, and 11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the wild‐type IDH1. Evaluation of the biological activities at the cellular level showed that compounds

  设计、合成了一系列 3-(7-azainodyl)-4-indolylmaleimides，并评估了它们的异柠檬酸脱氢酶 1 (IDH1)/R132H 抑制活性。许多化合物如 11a、11c、11e、11g 和 11s 对 IDH1/R132H 表现出良好的抑制作用，并且对野生型 IDH1 具有高度选择性。在细胞水平上对生物活性的评估表明，化合物 11a、11c、11e、11g 和 11s 可以有效抑制表达 IDH1/R132H 的 U87MG 细胞中 2-羟基戊二酸的产生。基于获得的实验数据讨论了初步构效关系 (SAR) 和分子建模研究。这些发现可能为开发新型 IDH1/R132H 抑制剂提供新的见解。