5-chloropyridin-3-yl 1H-indole-3-carboxylate | 1025906-65-3

• 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: 5-chloropyridin-3-yl 1H-indole-3-carboxylate
• 英文别名: acs.jmedchem.1c00409_ST.425；(5-chloropyridin-3-yl) 1H-indole-3-carboxylate
• CAS: 1025906-65-3
• 化学式: C₁₄H₉ClN₂O₂
• 分子量: 272.691
• InChiKey: YWKPSFBPBXOGRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-吲哚甲酸 、 5-氯-3-羟基吡啶 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以67%的产率得到5-chloropyridin-3-yl 1H-indole-3-carboxylate
  参考文献：
  名称：

  针对 SARS-CoV-2 的主要蛋白酶：从高通量筛选的建立到定制抑制剂的设计

  摘要：

  SARS-CoV-2 (M pro ) 的主要蛋白酶是 COVID-19 的病原体，是一个重要的药物靶点。一种新的荧光底物与内部淬灭的荧光肽进行了动力学比较，结果表明它非常适合用重组表达的 M pro进行高通量筛选。两类蛋白酶抑制剂，氮腈和吡啶酯，经过鉴定、优化并进行了深入的生化表征。配备独特氮腈弹头的定制肽同时抑制 M pro和组织蛋白酶 L（一种与病毒细胞进入相关的蛋白酶）。通过位置扫描分析吡啶基吲哚酯。事实证明，我们针对 M pro抑制剂的重点方法优于虚拟筛选。使用两种不可逆抑制剂，氮腈8 (k inac /K=37 500 m -1 s -1 , K=24.0 nm ) 和吡啶酯17 (k inac /K=29 100 m -1 s -1 , K=10.0 nm ），已经发现了有希望进一步开发的候选药物。

  DOI：

  10.1002/anie.202016961

文献信息

• Heteroaromatic ester inhibitors of hepatitis A virus 3C proteinase: Evaluation of mode of action
  作者：Carly Huitema、Jianmin Zhang、Jiang Yin、Michael N.G. James、John C. Vederas、Lindsay D. Eltis

  DOI：10.1016/j.bmc.2008.03.059

  日期：2008.5

  The related 3C and 3C-like proteinase (3C(pro) and 3CL(pro)) of picornaviruses and coronaviruses, respectively, are good drug targets. As part of an effort to generate broad-spectrum inhibitors of these enzymes, we screened a library of inhibitors based on a halopyridinyl ester from a previous study of the severe acute respiratory syndrome (SARS) 3CL proteinase against Hepatitis A virus (HAV) 3C(pro). Three of the compounds, which also had furan rings, inhibited the cleavage activity of HAV 3C(pro) with K-icS of 120-240 nM. HPLC-based assays revealed that the inhibitors were slowly hydrolyzed by both HAV 3C(pro) and SARS 3CL(pro), confirming the identity of the expected products. Mass spectrometric analyses indicated that this hydrolysis proceeded via an acylenzyme intermediate. Modeling studies indicated that the halopyridinyl moiety of the inhibitor fits tightly into the S1-binding pocket, consistent with the lack of tolerance of the inhibitors to modi. cation in this portion of the molecule. These compounds are among the most potent non-peptidic inhibitors reported to date against a 3C(pro). (C) 2008 Elsevier Ltd. All rights reserved.
• Targeting the Main Protease of SARS‐CoV‐2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors
  作者：Julian Breidenbach、Carina Lemke、Thanigaimalai Pillaiyar、Laura Schäkel、Ghazl Al Hamwi、Miriam Diett、Robin Gedschold、Nina Geiger、Vittoria Lopez、Salahuddin Mirza、Vigneshwaran Namasivayam、Anke C. Schiedel、Katharina Sylvester、Dominik Thimm、Christin Vielmuth、Lan Phuong Vu、Maria Zyulina、Jochen Bodem、Michael Gütschow、Christa E. Müller

  DOI：10.1002/anie.202016961

  日期：2021.4.26

  The main protease of SARS‐CoV‐2 (Mpro), the causative agent of COVID‐19, constitutes a significant drug target. A new fluorogenic substrate was kinetically compared to an internally quenched fluorescent peptide and shown to be ideally suitable for high throughput screening with recombinantly expressed Mpro. Two classes of protease inhibitors, azanitriles and pyridyl esters, were identified, optimized

  SARS-CoV-2 (M pro ) 的主要蛋白酶是 COVID-19 的病原体，是一个重要的药物靶点。一种新的荧光底物与内部淬灭的荧光肽进行了动力学比较，结果表明它非常适合用重组表达的 M pro进行高通量筛选。两类蛋白酶抑制剂，氮腈和吡啶酯，经过鉴定、优化并进行了深入的生化表征。配备独特氮腈弹头的定制肽同时抑制 M pro和组织蛋白酶 L（一种与病毒细胞进入相关的蛋白酶）。通过位置扫描分析吡啶基吲哚酯。事实证明，我们针对 M pro抑制剂的重点方法优于虚拟筛选。使用两种不可逆抑制剂，氮腈8 (k inac /K=37 500 m -1 s -1 , K=24.0 nm ) 和吡啶酯17 (k inac /K=29 100 m -1 s -1 , K=10.0 nm ），已经发现了有希望进一步开发的候选药物。