methyl [(2S)-3-methyl-1-oxo-1-{(2S,3aS,7aS)-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]octahydro-1H-indol-1-yl}butan-2-yl]carbamate | 1318897-25-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl [(2S)-3-methyl-1-oxo-1-{(2S,3aS,7aS)-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]octahydro-1H-indol-1-yl}butan-2-yl]carbamate
• 英文别名: methyl [(1S)-2-methyl-1-({(2S,3aS,7aS)-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]octahydro-1H-indol-1-yl}carbonyl)propyl]carbamate；methyl ((S)-3-methyl-1-oxo-1-((2S,3aS,7aS)-2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)octahydro-1H-indol-1-yl)butan-2-yl)carbamate；methyl N-[(2S)-1-[(2S,3aS,7aS)-2-[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]-2,3,3a,4,5,6,7,7a-octahydroindol-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 1318897-25-4
• 化学式: C₂₈H₄₁BN₄O₅
• 分子量: 524.468
• InChiKey: ASCNLISNAYEUJC-ZMVGRULKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  iodoferrocene 、 methyl [(2S)-3-methyl-1-oxo-1-{(2S,3aS,7aS)-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]octahydro-1H-indol-1-yl}butan-2-yl]carbamate 在 potassium phosphate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 3.0h， 以16%的产率得到(2-{(2S,3aS,7aS)-1-[N-(methoxycarbonyl)-L-valyl]octahydro-1H-indol-2-yl}-1H-benzimidazol-5-yl)ferrocene
  参考文献：
  名称：

  Ferrocene-based inhibitors of hepatitis C virus replication that target NS5A with low picomolar in vitro antiviral activity

  摘要：

  An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1'-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat.

  DOI：

  10.1016/j.bmcl.2018.09.023
• 作为产物：
  描述：

  4-溴邻苯二胺 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride potassium acetate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 methyl [(2S)-3-methyl-1-oxo-1-{(2S,3aS,7aS)-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazol-2-yl]octahydro-1H-indol-1-yl}butan-2-yl]carbamate
  参考文献：
  名称：

  [EN] CHEMICAL COMPOUNDS
  [FR] COMPOSÉS CHIMIQUES

  摘要：

  揭示了Formula II的化合物。还披露了这些化合物的盐、包含这些化合物或盐的药物组合物，以及通过给予这些化合物或盐来治疗HCV感染的方法。

  公开号：

  WO2011091446A1

文献信息

• SUBSITUTED ALIPHANES, CYCLOPHANES, HETERAPHANES, HETEROPHANES, HETERO-HETERAPHANES AND METALLOCENES USEFUL FOR TREATING HCV INFECTIONS
  申请人：Wiles Jason Allan

  公开号：US20120302538A1

  公开（公告）日：2012-11-29

  The present disclosure provides substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes, of Formula I D-M-D  (Formula I) useful as antiviral agents. In certain embodiments disclosed herein M is a group —P-A-P— where A is Certain substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions/ and combinations containing one or more substituted aliphanes, cyclophanes, heteraphanes, heterophanes, hetero-heteraphanes and metallocenes and a pharmaceutically acceptable carrier are also provided by this disclosure. Methods for treating viral infections, including Hepatitis C viral infections are provided by the disclosure.

  本公开提供了替代脂环烷、环烷、杂环烷、杂脂环烷、杂杂环烷和金属茂的化合物，其化学式为ID-M-D（化学式I），用作抗病毒剂。在本公开的某些实施例中，M是一个基团—P-A-P—，其中A是。本公开披露的某些替代脂环烷、环烷、杂环烷、杂脂环烷、杂杂环烷和金属茂是病毒复制的有效和/或选择性抑制剂，特别是对乙型肝炎病毒复制。本公开还提供了含有一种或多种替代脂环烷、环烷、杂环烷、杂脂环烷、杂杂环烷和金属茂以及药用载体的药物组合物/和配方。本公开提供了治疗病毒感染，包括乙型肝炎病毒感染的方法。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011091446A1

  公开（公告）日：2011-07-28

  Disclosed are compounds of Formula II. Also disclosed are salts of the compounds, pharmaceutical compositions comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts.

  揭示了Formula II的化合物。还披露了这些化合物的盐、包含这些化合物或盐的药物组合物，以及通过给予这些化合物或盐来治疗HCV感染的方法。
• Ferrocene-based inhibitors of hepatitis C virus replication that target NS5A with low picomolar in vitro antiviral activity
  作者：Venkat R. Gadhachanda、Kyle J. Eastman、Qiuping Wang、Avinash S. Phadke、Dharaben Patel、Wengang Yang、Christopher W. Marlor、Milind Deshpande、Mingjun Huang、Jason A. Wiles

  DOI：10.1016/j.bmcl.2018.09.023

  日期：2018.11

  An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1'-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat.