5-Fluoro-6-((Z)-1-phenyl-but-1-en-3-ynyl)-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine

• 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: 5-Fluoro-6-((Z)-1-phenyl-but-1-en-3-ynyl)-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine
• 英文别名: 5-fluoro-6-(1-phenylbut-1-en-3-ynyl)-1-propan-2-ylsulfonylbenzimidazol-2-amine
• 化学式: C₂₀H₁₈FN₃O₂S
• 分子量: 383.446
• InChiKey: LEOVSGGLBVOTQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.41
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.98
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  5-氯-4-氟-2-硝基苯胺 在 镍 吡啶 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 potassium tert-butylate 、 水 、 氢气 、 双氧水 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 、 乙腈 为溶剂， 25.0 ℃ 、413.69 kPa 条件下， 反应 26.0h， 生成 5-Fluoro-6-((Z)-1-phenyl-but-1-en-3-ynyl)-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine
  参考文献：
  名称：

  Antirhino/Enteroviral Vinylacetylene Benzimidazoles:  A Study of Their Activity and Oral Plasma Levels in Mice

  摘要：

  In an effort to find an orally bioavailable antiviral for the treatment of rhino/enteroviral infections, a series of vinylacetylene benzimidazoles (11a-o, 12, and 18a was made. Initial studies of this class of antivirals showed that fluorine substitution on the left-hand phenyl ring in combination with the vinylacetylene moiety gave the requisite mix of physical properties to achieve good in vitro antiviral activity as well as respectable oral bioavailability in rhesus monkeys. To ascertain the generality of this finding and to broaden the scope of the structure-activity relationship (SAR), the present study concentrated on fluoro substitution of this class of molecules. The initial antiviral activity for each analogue was measured using human rhinovirus 14 (HRV-14). This served as an indicator of general antiviral activity for SAR purposes. Subsequently, the spectrum of antirhino/enteroviral activity of the more interesting analogues was evaluated through testing against a panel of seven additional rhino/enteroviruses. Broad-spectrum activity was present and consistent for all analogues tested, and it tracked closely with the antiviral activity observed against HRV-14. A simple screening protocol for oral bioavailability was established whereby compounds were administered orally to mice and plasma levels were measured. This procedure facilitated the evaluation of numerous analogues in a rapid manner. The C-max was used as a measure of oral bioavailability to allow relative ranking of compounds. In general, fluorine substitution directly on the left-hand aromatic ring does give good oral blood levels. However, fluorine incorporation at other positions in the molecule was not as effective at maintaining either the activity or the oral plasma levels. The constructive combination of activity and oral plasma levels was maximized in three derivatives: 11a,e,g.

  DOI：

  10.1021/jm970423k

文献信息

• Antirhino/Enteroviral Vinylacetylene Benzimidazoles:  A Study of Their Activity and Oral Plasma Levels in Mice
  作者：Mark J. Tebbe、Wayne A. Spitzer、Frantz Victor、Shawn C. Miller、Chris C. Lee、Thomas R. Sattelberg、Emma McKinney、Joseph C. Tang

  DOI：10.1021/jm970423k

  日期：1997.11.1

  In an effort to find an orally bioavailable antiviral for the treatment of rhino/enteroviral infections, a series of vinylacetylene benzimidazoles (11a-o, 12, and 18a was made. Initial studies of this class of antivirals showed that fluorine substitution on the left-hand phenyl ring in combination with the vinylacetylene moiety gave the requisite mix of physical properties to achieve good in vitro antiviral activity as well as respectable oral bioavailability in rhesus monkeys. To ascertain the generality of this finding and to broaden the scope of the structure-activity relationship (SAR), the present study concentrated on fluoro substitution of this class of molecules. The initial antiviral activity for each analogue was measured using human rhinovirus 14 (HRV-14). This served as an indicator of general antiviral activity for SAR purposes. Subsequently, the spectrum of antirhino/enteroviral activity of the more interesting analogues was evaluated through testing against a panel of seven additional rhino/enteroviruses. Broad-spectrum activity was present and consistent for all analogues tested, and it tracked closely with the antiviral activity observed against HRV-14. A simple screening protocol for oral bioavailability was established whereby compounds were administered orally to mice and plasma levels were measured. This procedure facilitated the evaluation of numerous analogues in a rapid manner. The C-max was used as a measure of oral bioavailability to allow relative ranking of compounds. In general, fluorine substitution directly on the left-hand aromatic ring does give good oral blood levels. However, fluorine incorporation at other positions in the molecule was not as effective at maintaining either the activity or the oral plasma levels. The constructive combination of activity and oral plasma levels was maximized in three derivatives: 11a,e,g.