1-{[4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl]carbonyl}piperidine-4-carboxylic acid | 903165-63-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-{[4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl]carbonyl}piperidine-4-carboxylic acid
• 英文别名: 1-[4-[(4-chlorophenyl)methyl]thieno[3,2-b]pyrrole-5-carbonyl]piperidine-4-carboxylic acid
• CAS: 903165-63-9
• 化学式: C₂₀H₁₉ClN₂O₃S
• mdl: MFCD14280420
• 分子量: 402.901
• InChiKey: JVFNHKSESNNPPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  90.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-{[4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl]carbonyl}piperidine-4-carboxylic acid 、 R(+)-alpha-甲基苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 生成 (R)-1-(4-(4-fluorobenzyl)-4H-thieno[3,2-b]pyrrole-5-carbonyl)-N-(1-phenylethyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis

  摘要：

  Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.

  DOI：

  10.1021/jm300214e
• 作为产物：
  描述：

  4H-噻吩并[3,2-b]吡咯-5-羧酸甲酯 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.5h， 生成 1-{[4-(4-chlorobenzyl)-4H-thieno[3,2-b]pyrrol-5-yl]carbonyl}piperidine-4-carboxylic acid
  参考文献：
  名称：

  Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis

  摘要：

  Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.

  DOI：

  10.1021/jm300214e

文献信息

• US8486945B2
  申请人：——

  公开号：US8486945B2

  公开（公告）日：2013-07-16
• Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis
  作者：Janice A. Sindac、Bryan D. Yestrepsky、Scott J. Barraza、Kyle L. Bolduc、Pennelope K. Blakely、Richard F. Keep、David N. Irani、David J. Miller、Scott D. Larsen

  DOI：10.1021/jm300214e

  日期：2012.4.12

  Arboviral encephalitis is a potentially devastating human disease with no approved therapies that target virus replication. We previously discovered a novel class of thieno[3,2-b]pyrrole-based inhibitors active against neurotropic alphaviruses such as western equine encephalitis virus (WEEV) in cultured cells. In this report, we describe initial development of these novel antiviral compounds, including bioisosteric replacement of the 4H-thieno[3,2-b]pyrrole core with indole to improve metabolic stability and the introduction of chirality to assess target enantioselectivity. Selected modifications enhanced antiviral activity while maintaining low cytotoidcity, increased stability to microsomal metabolism, and also revealed striking enantiospecific activity in cultured cells. Furthermore, we demonstrate improved outcomes (both symptoms and survival) following treatment with indole analogue 9h (CCG-203926) in an in vivo mouse model of alphaviral encephalitis that closely correlate with the enantiospecific in vitro antiviral activity. These results represent a substantial advancement in the early preclinical development of a promising class of novel antiviral drugs against virulent neurotropic alphaviruses.