1-isopropylsulfonyl-2-amino-6-(2,5-difluorobenzoyl)benzimidazole | 180601-51-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-isopropylsulfonyl-2-amino-6-(2,5-difluorobenzoyl)benzimidazole
• 英文别名: (2-amino-3-propan-2-ylsulfonylbenzimidazol-5-yl)-(2,5-difluorophenyl)methanone
• CAS: 180601-51-8
• 化学式: C₁₇H₁₅F₂N₃O₃S
• 分子量: 379.387
• InChiKey: TXNKFNLFPJMZLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-isopropylsulfonyl-2-amino-6-(2,5-difluorobenzoyl)benzimidazole 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 水 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 5.0h， 生成 6-[(E)-1-(2,5-Difluoro-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
• 作为产物：
  描述：

  2-硝基-5-氯苯胺 在 镍 吡啶 、 sodium hydroxide 、 potassium tert-butylate 、 氢气 、 双氧水 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 25.0 ℃ 、413.69 kPa 条件下， 反应 21.0h， 生成 1-isopropylsulfonyl-2-amino-6-(2,5-difluorobenzoyl)benzimidazole
  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

• Anti-viral compounds
  申请人：Eli Lilly and Company

  公开号：US06114327A1

  公开（公告）日：2000-09-05

  The present application provides a series of benzimidazole compounds of formula I: ##STR1## which inhibit the growth of picornaviruses, such as rhinoviruses (bovine and human), enteroviruses such as polioviruses, coxsackieviruses of the A and B groups, or echo virus, cardioviruses such as encephalomyocarditis (EMC), apthoviruses such as foot and mouth disease virus, and flaviviruses such as hepatitis C virus and bovine viral diarrhea virus. Such compounds are also useful as intermediates for preparing additional benzimidazole antiviral compounds.

  本申请提供了一系列式I的苯并咪唑化合物：##STR1## 这些化合物抑制了小肠病毒的生长，例如鼻病毒（牛和人类）、脊髓灰质炎病毒、A和B组的柯萨奇病毒、回声病毒、心病毒如脑心肌炎病毒（EMC）、口蹄疫病毒、肝炎C病毒和牛病毒性腹泻病毒等黄病毒。这些化合物也可用作制备额外的苯并咪唑抗病毒化合物的中间体。
• US6114327A
  申请人：——

  公开号：US6114327A

  公开（公告）日：2000-09-05