4-(2-(chloromethyl)-1H-benzo[d]imidazol-1-yl)butanenitrile | 752975-92-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4-(2-(chloromethyl)-1H-benzo[d]imidazol-1-yl)butanenitrile
• 英文别名: 4-(2-chloromethyl-benzoimidazol-1-yl)-butyronitrile；4-[2-(chloromethyl)benzimidazol-1-yl]butanenitrile
• CAS: 752975-92-1
• 化学式: C₁₂H₁₂ClN₃
• 分子量: 233.7
• InChiKey: IXQZSKXKAVRCLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  2-羟甲基苯并咪唑 在 氯化亚砜 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.25h， 生成 4-(2-(chloromethyl)-1H-benzo[d]imidazol-1-yl)butanenitrile
  参考文献：
  名称：

  [EN] INHIBITORS OF RSV REPLICATION AND APPLICATIONS THEREOF
  [FR] INHIBITEURS DE LA RÉPLICATION DU VIRUS RESPIRATOIRE SYNCYTIAL (VRS) ET LEURS UTILISATIONS

  摘要：

  本文提供了一种根据式（A）或其盐制备的化合物，用于治疗RSV感染。还提供了使用式（A）化合物治疗病毒RSV感染的方法，可选择性地与一种或多种其他抗病毒药物结合使用，以及含有式（A）化合物和可选择性地一种或多种其他抗病毒药物的药物组合物。

  公开号：

  WO2019046364A1

文献信息

• Benzimidazolone antiviral agents
  申请人：Bristol-Myers Squibb Company

  公开号：US06506738B1

  公开（公告）日：2003-01-14

  The present invention concerns antiviral compounds, their compositions, and use in the treatment of viral infections. More particularly, the invention provides benzimidazolone derivatives for the treatment of respiratory syncytial virus infection.

  本发明涉及抗病毒化合物，它们的组成以及在治疗病毒感染中的用途。更具体地，本发明提供苯并咪唑酮衍生物用于治疗呼吸道合胞病毒感染。
• US6506738B1
  申请人：——

  公开号：US6506738B1

  公开（公告）日：2003-01-14
• US6774134B2
  申请人：——

  公开号：US6774134B2

  公开（公告）日：2004-08-10
• 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.
• [EN] INHIBITORS OF RSV REPLICATION AND APPLICATIONS THEREOF<br/>[FR] INHIBITEURS DE LA RÉPLICATION DU VIRUS RESPIRATOIRE SYNCYTIAL (VRS) ET LEURS UTILISATIONS
  申请人：UNIV EMORY

  公开号：WO2019046364A1

  公开（公告）日：2019-03-07

  A compound according to Formula (A) or salt thereof, for use in the treatment of RSV infections is provided herein. Also provided is a method of treating viral RSV infections using compounds of Formula (A), optionally in combination with one or more other antiviral agents as well as pharmaceutical compositions containing a compound of Formula (A) and optionally one or more other antiviral agents.

  本文提供了一种根据式（A）或其盐制备的化合物，用于治疗RSV感染。还提供了使用式（A）化合物治疗病毒RSV感染的方法，可选择性地与一种或多种其他抗病毒药物结合使用，以及含有式（A）化合物和可选择性地一种或多种其他抗病毒药物的药物组合物。