N-(4-chlorobenzyl)-7-methyl-4-oxo-2-vinyl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide | 863102-01-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: N-(4-chlorobenzyl)-7-methyl-4-oxo-2-vinyl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide
• 英文别名: N-[(4-chlorophenyl)methyl]-2-ethenyl-7-methyl-4-oxothieno[2,3-b]pyridine-5-carboxamide
• CAS: 863102-01-6
• 化学式: C₁₈H₁₅ClN₂O₂S
• 分子量: 358.848
• InChiKey: JKAXTBGLKVRZPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-chlorobenzyl)-7-methyl-4-oxo-2-vinyl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide 在 9-硼双环[3.3.1]壬烷 、 sodium hydroxide 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 以11%的产率得到N-[(4-chlorophenyl)methyl]-2-(2-hydroxyethyl)-7-methyl-4-oxo-thieno[2,3-b]pyridine-5-carboxamide
  参考文献：
  名称：

  4-Oxo-4,7-dihydrothieno[2,3-b]pyridines as Non-Nucleoside Inhibitors of Human Cytomegalovirus and Related Herpesvirus Polymerases

  摘要：

  A novel series of 4-oxo-4,7-dihydrothieno[2,3-blpyridine-5-carboxamides have been identified as potential antivirals against human herpesvirus infections resulting from human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV). Compounds 10c and 14 demonstrated broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, and VZV. High specificity for the viral polymerases was observed compared to human alpha polyinerase. The antiviral activity of 10c and 14, as determined by plaque reduction assay, was comparable or superior to that of existing antiherpes drugs, ganciclovir (for HCMV) and acyclovir (for HSV-1 and VZV). Drug resistance to compound 14 correlated to point mutations in conserved domain III of the herpesvirus DNA polymerase, but these mutations do not confer resistance to existing nucleoside therapy. In addition, compound 14 maintained potent antiviral activity against acyclovir-resistant HSV-1 strains. Substitution to the pyridone nitrogen (N7) was found to be critical for enhanced in vitro antiviral activity.

  DOI：

  10.1021/jm050162b
• 作为产物：
  描述：

  4-羟基噻吩并[3,2-B]吡啶-5-甲酸乙酯 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium acetate 、 一氯化碘 、 potassium carbonate 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 N-(4-chlorobenzyl)-7-methyl-4-oxo-2-vinyl-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide
  参考文献：
  名称：

  4-Oxo-4,7-dihydrothieno[2,3-b]pyridines as Non-Nucleoside Inhibitors of Human Cytomegalovirus and Related Herpesvirus Polymerases

  摘要：

  A novel series of 4-oxo-4,7-dihydrothieno[2,3-blpyridine-5-carboxamides have been identified as potential antivirals against human herpesvirus infections resulting from human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV). Compounds 10c and 14 demonstrated broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, and VZV. High specificity for the viral polymerases was observed compared to human alpha polyinerase. The antiviral activity of 10c and 14, as determined by plaque reduction assay, was comparable or superior to that of existing antiherpes drugs, ganciclovir (for HCMV) and acyclovir (for HSV-1 and VZV). Drug resistance to compound 14 correlated to point mutations in conserved domain III of the herpesvirus DNA polymerase, but these mutations do not confer resistance to existing nucleoside therapy. In addition, compound 14 maintained potent antiviral activity against acyclovir-resistant HSV-1 strains. Substitution to the pyridone nitrogen (N7) was found to be critical for enhanced in vitro antiviral activity.

  DOI：

  10.1021/jm050162b

文献信息

• 4-Oxo-4,7-dihydrothieno[2,3-<i>b</i>]pyridines as Non-Nucleoside Inhibitors of Human Cytomegalovirus and Related Herpesvirus Polymerases
  作者：Mark E. Schnute、Michele M. Cudahy、Roger J. Brideau、Fred L. Homa、Todd A. Hopkins、Mary L. Knechtel、Nancee L. Oien、Thomas W. Pitts、Roger A. Poorman、Michael W. Wathen、Janet L. Wieber

  DOI：10.1021/jm050162b

  日期：2005.9.1

  A novel series of 4-oxo-4,7-dihydrothieno[2,3-blpyridine-5-carboxamides have been identified as potential antivirals against human herpesvirus infections resulting from human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV). Compounds 10c and 14 demonstrated broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, and VZV. High specificity for the viral polymerases was observed compared to human alpha polyinerase. The antiviral activity of 10c and 14, as determined by plaque reduction assay, was comparable or superior to that of existing antiherpes drugs, ganciclovir (for HCMV) and acyclovir (for HSV-1 and VZV). Drug resistance to compound 14 correlated to point mutations in conserved domain III of the herpesvirus DNA polymerase, but these mutations do not confer resistance to existing nucleoside therapy. In addition, compound 14 maintained potent antiviral activity against acyclovir-resistant HSV-1 strains. Substitution to the pyridone nitrogen (N7) was found to be critical for enhanced in vitro antiviral activity.