4-[2-[(2-Oxo-3-trityloxyiminopyrrolo[2,3-b]pyridin-1-yl)methyl]benzimidazol-1-yl]butanenitrile | 443986-74-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-[2-[(2-Oxo-3-trityloxyiminopyrrolo[2,3-b]pyridin-1-yl)methyl]benzimidazol-1-yl]butanenitrile
• 英文别名: 4-[2-[(2-oxo-3-trityloxyiminopyrrolo[2,3-b]pyridin-1-yl)methyl]benzimidazol-1-yl]butanenitrile
• CAS: 443986-74-1
• 化学式: C₃₈H₃₀N₆O₂
• 分子量: 602.695
• InChiKey: FULRQOCFIRBPQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  96.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[2-[(2-Oxo-3-trityloxyiminopyrrolo[2,3-b]pyridin-1-yl)methyl]benzimidazol-1-yl]butanenitrile 生成 4-[2-[(3-hydroxyimino-2-oxopyrrolo[2,3-b]pyridin-1-yl)methyl]benzimidazol-1-yl]butanenitrile
  参考文献：
  名称：

  Respiratory syncytial virus fusion inhibitors. Part 7: Structure–activity relationships associated with a series of isatin oximes that demonstrate antiviral activity in vivo

  摘要：

  A series of bezimidazole-isatin oximes were prepared and profiled as inhibitors of respiratory syncytial virus (RSV) replication in cell culture. Structure-activity relationship studies were directed toward optimization of antiviral activity, cell permeability and metabolic stability in human liver micorosomes (HLM). Parallel combinatorial synthetic chemistry was employed to functionalize isatin oximes via O-alkylation which quickly identified a subset of small, lipophilic substituents that established good potency for the series. Further optimization of the isatin oxime derivatives focused on introduction of nitrogen atoms to the isatin phenyl ring to provide a series of aza-isatin oximes with significantly improved PK properties. Several aza-isatin oximes analogs displayed targeted metabolic stability in HLM and permeability across a confluent monolayer of CaCo-2 cells. These studies identified several compounds, including 18i, 18j and 18n that demonstrated antiviral activity in the BALB/c mouse model of RSV infection following oral dosing. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.030
• 作为产物：
  描述：

  4-(2-(chloromethyl)-1H-benzo[d]imidazol-1-yl)butanenitrile 、 (3Z)-3-trityloxyimino-1H-pyrrolo[2,3-b]pyridin-2-one 在 caesium carbonate 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 4-[2-[(2-Oxo-3-trityloxyiminopyrrolo[2,3-b]pyridin-1-yl)methyl]benzimidazol-1-yl]butanenitrile
  参考文献：
  名称：

  Respiratory syncytial virus fusion inhibitors. Part 7: Structure–activity relationships associated with a series of isatin oximes that demonstrate antiviral activity in vivo

  摘要：

  A series of bezimidazole-isatin oximes were prepared and profiled as inhibitors of respiratory syncytial virus (RSV) replication in cell culture. Structure-activity relationship studies were directed toward optimization of antiviral activity, cell permeability and metabolic stability in human liver micorosomes (HLM). Parallel combinatorial synthetic chemistry was employed to functionalize isatin oximes via O-alkylation which quickly identified a subset of small, lipophilic substituents that established good potency for the series. Further optimization of the isatin oxime derivatives focused on introduction of nitrogen atoms to the isatin phenyl ring to provide a series of aza-isatin oximes with significantly improved PK properties. Several aza-isatin oximes analogs displayed targeted metabolic stability in HLM and permeability across a confluent monolayer of CaCo-2 cells. These studies identified several compounds, including 18i, 18j and 18n that demonstrated antiviral activity in the BALB/c mouse model of RSV infection following oral dosing. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.030

文献信息

• Respiratory syncytial virus fusion inhibitors. Part 7: Structure–activity relationships associated with a series of isatin oximes that demonstrate antiviral activity in vivo
  作者：Ny Sin、Brian L. Venables、Keith D. Combrink、H. Belgin Gulgeze、Kuo-Long Yu、Rita L. Civiello、Jan Thuring、X. Alan Wang、Zheng Yang、Lisa Zadjura、Anthony Marino、Kathleen F. Kadow、Christopher W. Cianci、Junius Clarke、Eugene V. Genovesi、Ivette Medina、Lucinda Lamb、Mark Krystal、Nicholas A. Meanwell

  DOI：10.1016/j.bmcl.2009.06.030

  日期：2009.8

  A series of bezimidazole-isatin oximes were prepared and profiled as inhibitors of respiratory syncytial virus (RSV) replication in cell culture. Structure-activity relationship studies were directed toward optimization of antiviral activity, cell permeability and metabolic stability in human liver micorosomes (HLM). Parallel combinatorial synthetic chemistry was employed to functionalize isatin oximes via O-alkylation which quickly identified a subset of small, lipophilic substituents that established good potency for the series. Further optimization of the isatin oxime derivatives focused on introduction of nitrogen atoms to the isatin phenyl ring to provide a series of aza-isatin oximes with significantly improved PK properties. Several aza-isatin oximes analogs displayed targeted metabolic stability in HLM and permeability across a confluent monolayer of CaCo-2 cells. These studies identified several compounds, including 18i, 18j and 18n that demonstrated antiviral activity in the BALB/c mouse model of RSV infection following oral dosing. (C) 2009 Elsevier Ltd. All rights reserved.