3-cyclohexyl-2-furan-3-yl-1-methyl-1H-indole-6-carboxylic acid | 494799-77-8

• 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: 3-cyclohexyl-2-furan-3-yl-1-methyl-1H-indole-6-carboxylic acid
• 英文别名: 3-cyclohexyl-2-(furan-3-yl)-1-methylindole-6-carboxylic acid
• CAS: 494799-77-8
• 化学式: C₂₀H₂₁NO₃
• 分子量: 323.392
• InChiKey: SOOVFVIRAAYMHK-UHFFFAOYSA-N

物化性质

• 沸点：
  543.9±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-cyclohexyl-2-furan-3-yl-1-methyl-1H-indole-6-carboxylic acid 在 N,N-二甲基甲酰胺 氯化亚砜 、 N,O-双三甲硅基羟胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-cyclohexyl-2-(furan-3-yl)-N-hydroxy-1-methylindole-6-carboxamide
  参考文献：
  名称：

  Inhibitors of HCV replication

  摘要：

  揭示了具有结构式（I）的化合物。这些化合物可以抑制丙型肝炎病毒（HCV）的复制，特别是HCV NS5B蛋白的功能。

  公开号：

  US20050119318A1
• 作为产物：
  描述：

  3-环己烷吲哚-6-甲酸 在 sodium hydroxide 、 四(三苯基膦)钯 、 pyridinium hydrobromide perbromide 、 sodium hydride 、 sodium carbonate 、 potassium carbonate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 20.0h， 生成 3-cyclohexyl-2-furan-3-yl-1-methyl-1H-indole-6-carboxylic acid
  参考文献：
  名称：

  改善 HCV NS5B 聚合酶非核苷变构抑制剂的复制子细胞活性：从苯并咪唑到吲哚支架。

  摘要：

  基于苯并咪唑的丙型肝炎病毒 (HCV) NS5B 聚合酶变构抑制剂被多样化用于各种拓扑相关的支架。用亲脂性吲哚取代极性苯并咪唑核心导致抑制剂在基于细胞的亚基因组 HCV 复制子系统中具有更高的效力。将吲哚支架转移到先前描述的一系列苯并咪唑-色氨酸酰胺中产生了迄今为止在该系列中报告的细胞培养物中最有效的 HCV RNA 复制抑制剂（EC(50) 约 50 nM）。

  DOI：

  10.1016/j.bmcl.2006.07.074

文献信息

• Importance of Ligand Bioactive Conformation in the Discovery of Potent Indole-Diamide Inhibitors of the Hepatitis C Virus NS5B
  作者：Steven R. LaPlante、James R. Gillard、Araz Jakalian、Norman Aubry、René Coulombe、Christian Brochu、Youla S. Tsantrizos、Martin Poirier、George Kukolj、Pierre L. Beaulieu

  DOI：10.1021/ja101358s

  日期：2010.11.3

  Significant advances have led to receptor induced-fit and conformational selection models for describing bimolecular recognition, but a more comprehensive view must evolve to also include ligand shape and conformational changes. Here, we describe an example where a ligand's "structural hinge" influences potency by inducing an "L-shape" bioactive conformation, and due to its solvent exposure in the complex, reasonable conformation-activity-relationships can be qualitatively attributed. From a ligand design perspective, this feature was exploited by successful linker hopping to an alternate "structural hinge" that led to a new and promising chemical series which matched the ligand bioactive conformation and the pocket bioactive space. Using a combination of X-ray crystallography, NMR and modeling with support from binding-site resistance mutant studies and photoaffinity labeling experiments, we were able to derive inhibitor-polymerase complexes for various chemical series.
• From benzimidazole to indole-5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase. Part 1: Indole C-2 SAR and discovery of diamide derivatives with nanomolar potency in cell-based subgenomic replicons
  作者：Pierre L. Beaulieu、James Gillard、Eric Jolicoeur、Jianmin Duan、Michel Garneau、George Kukolj、Marc-André Poupart

  DOI：10.1016/j.bmcl.2011.04.059

  日期：2011.6

  Replacement of the benzimidazole core of allosteric Thumb Pocket 1 HCV NS5B finger loop inhibitors by more lipophilic indole derivatives provided up to 30-fold potency improvements in cell-based subgenomic replicon assays. Optimization of C-2 substitution on the indole core led to the identification of analogs with EC50 <100 nM and modulated the pharmacokinetic properties of the inhibitors based on preliminary data from in vitro ADME profiles and in vivo rat PK. (C) 2011 Elsevier Ltd. All rights reserved.
• Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCV NS5B polymerase: From benzimidazole to indole scaffolds
  作者：Pierre L. Beaulieu、James Gillard、Darren Bykowski、Christian Brochu、Nathalie Dansereau、Jean-Simon Duceppe、Bruno Haché、Araz Jakalian、Lisette Lagacé、Steven LaPlante、Ginette McKercher、Elaine Moreau、Stéphane Perreault、Timothy Stammers、Louise Thauvette、Jeff Warrington、George Kukolj

  DOI：10.1016/j.bmcl.2006.07.074

  日期：2006.10

  Benzimidazole-based allosteric inhibitors of the hepatitis C virus (HCV) NS5B polymerase were diversified to a variety of topologically related scaffolds. Replacement of the polar benzimidazole core by lipophilic indoles led to inhibitors with improved potency in the cell-based subgenomic HCV replicon system. Transposing the indole scaffold into a previously described series of benzimidazole-tryptophan

  基于苯并咪唑的丙型肝炎病毒 (HCV) NS5B 聚合酶变构抑制剂被多样化用于各种拓扑相关的支架。用亲脂性吲哚取代极性苯并咪唑核心导致抑制剂在基于细胞的亚基因组 HCV 复制子系统中具有更高的效力。将吲哚支架转移到先前描述的一系列苯并咪唑-色氨酸酰胺中产生了迄今为止在该系列中报告的细胞培养物中最有效的 HCV RNA 复制抑制剂（EC(50) 约 50 nM）。
• Inhibitors of HCV replication
  申请人：Hudyma W. Thomas

  公开号：US20050119318A1

  公开（公告）日：2005-06-02

  Compounds having the structure of formula (I) are disclosed. The compounds can inhibit hepatitis C virus (HCV) replication, and in particular the function of the HCV NS5B protein.

  揭示了具有结构式（I）的化合物。这些化合物可以抑制丙型肝炎病毒（HCV）的复制，特别是HCV NS5B蛋白的功能。