2-isopropylamino-4,5,6-trichlorobenzimidazole | 193527-04-7

• 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: 2-isopropylamino-4,5,6-trichlorobenzimidazole
• 英文别名: 2-(Isopropylamino)-4,5,6-trichloro-1H-benzimidazole；4,5,6-trichloro-N-propan-2-yl-1H-benzimidazol-2-amine
• CAS: 193527-04-7
• 化学式: C₁₀H₁₀Cl₃N₃
• 分子量: 278.568
• InChiKey: DUCXIEGUVNUKRF-UHFFFAOYSA-N

物化性质

• 沸点：
  415.2±55.0 °C(Predicted)
• 密度：
  1.515±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-isopropylamino-4,5,6-trichlorobenzimidazole 在 三氟甲磺酸三甲基硅酯 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 16.5h， 生成 2-isopropylamino-4,5,6-trichloro-1-(β-L-erythrofuranosyl)benzimidazole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Halogenated β-d- and -l-Erythrofuranosylbenzimidazoles

  摘要：

  A series of 2-substituted benzimidazole D- and L-erythrofuranosyl nucleosides were synthesized and tested for activity against herpesviruses and for cytotoxicity. The D-nucleosides 2,5,6-trichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8a) and 2-bromo-5,6-dichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8b) were prepared by coupling 1,2,3,-tri-O-acetyl-beta-D-erythrofuranose (D-6) with the appropriate benzimidazole, followed by removal of the acetyl protecting groups. The 2-isopropylamino (9), 2-cyclopropylamino (10), and 2-mercaptobenzyl (11) derivatives were synthesized by nucleophilic displacements of the C-2 chlorine in the benzimidazole moiety of 8a. The D-nucleoside 4-bromo-5,6-dichloro-2-isopropylamino-1-(beta-D-erythrofuranosyl)benzimidazole (17) was prepared by coupling D-6 with the appropriate benzimidazole. The L-erythrofuranosyl derivatives, 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a), its 2-cyclopropylamine analogue (21b), and the 2-isopropylamino analogue (4c). In comparison, 8a was 15-fold more active against HCMV than 4a, and 8b was 4-fold more active against HCMV than 4b. The 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a) was less active than 4c, which is now in clinical trials for HCMV infection. Both 8a,b had comparable HCMV activity to 4c. Mode of action studies with the D-erythrose analogues established that 8b acted by inhibition of viral DNA processing whereas 9 and 10 may act via a different mechanism. The lack of a 5'-hydroxymethyl group in all members of this series established that antiviral activity occurred without 5'-phosphorylation, a feature required for the activity of most nucleoside analogues.

  DOI：

  10.1021/jm990195p
• 作为产物：
  描述：

  4,5-二氯-2-硝基苯胺 在 吡啶 、 盐酸 、 N-氯代丁二酰亚胺 、 1-环已基-2-吗啉乙基碳二亚胺对甲苯磺酸盐 、 铁粉 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 2-isopropylamino-4,5,6-trichlorobenzimidazole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Halogenated β-d- and -l-Erythrofuranosylbenzimidazoles

  摘要：

  A series of 2-substituted benzimidazole D- and L-erythrofuranosyl nucleosides were synthesized and tested for activity against herpesviruses and for cytotoxicity. The D-nucleosides 2,5,6-trichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8a) and 2-bromo-5,6-dichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8b) were prepared by coupling 1,2,3,-tri-O-acetyl-beta-D-erythrofuranose (D-6) with the appropriate benzimidazole, followed by removal of the acetyl protecting groups. The 2-isopropylamino (9), 2-cyclopropylamino (10), and 2-mercaptobenzyl (11) derivatives were synthesized by nucleophilic displacements of the C-2 chlorine in the benzimidazole moiety of 8a. The D-nucleoside 4-bromo-5,6-dichloro-2-isopropylamino-1-(beta-D-erythrofuranosyl)benzimidazole (17) was prepared by coupling D-6 with the appropriate benzimidazole. The L-erythrofuranosyl derivatives, 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a), its 2-cyclopropylamine analogue (21b), and the 2-isopropylamino analogue (4c). In comparison, 8a was 15-fold more active against HCMV than 4a, and 8b was 4-fold more active against HCMV than 4b. The 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a) was less active than 4c, which is now in clinical trials for HCMV infection. Both 8a,b had comparable HCMV activity to 4c. Mode of action studies with the D-erythrose analogues established that 8b acted by inhibition of viral DNA processing whereas 9 and 10 may act via a different mechanism. The lack of a 5'-hydroxymethyl group in all members of this series established that antiviral activity occurred without 5'-phosphorylation, a feature required for the activity of most nucleoside analogues.

  DOI：

  10.1021/jm990195p

文献信息

• L-benzimidazole nucleosides
  申请人：Glaxo Wellcome Inc.

  公开号：US06204249B1

  公开（公告）日：2001-03-20

  The present invention relates to benzimidazole derivatives and their use in medical therapy particularly for the treatment or prophylaxis of virus infections such as those caused by herpes viruses. The invention also relates to the preparation of the benzimidazole derivatives and pharmaceutical formulations containing them.

  本发明涉及苯并咪唑衍生物及其在医学疗法中的应用，特别是用于治疗或预防病毒感染，如由疱疹病毒引起的感染。该发明还涉及苯并咪唑衍生物的制备以及含有它们的药物配方。
• Therapeutic compounds
  申请人：——

  公开号：US06617315B1

  公开（公告）日：2003-09-09

  The present invention relates to benzimidazole derivatives and their use in medical therapy particularly for the treatment or prophylaxis of restenosis.

  本发明涉及苯并咪唑衍生物及其在医学治疗中的应用，特别是用于治疗或预防再狭窄。
• US6204249B1
  申请人：——

  公开号：US6204249B1

  公开（公告）日：2001-03-20
• US6617315B1
  申请人：——

  公开号：US6617315B1

  公开（公告）日：2003-09-09
• Synthesis and Antiviral Evaluation of Halogenated β-<scp>d</scp>- and -<scp>l</scp>-Erythrofuranosylbenzimidazoles
  作者：Kristjan S. Gudmundsson、Jeffrey Tidwell、Nicole Lippa、George W. Koszalka、Nanine van Draanen、Roger G. Ptak、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm990195p

  日期：2000.6.1

  A series of 2-substituted benzimidazole D- and L-erythrofuranosyl nucleosides were synthesized and tested for activity against herpesviruses and for cytotoxicity. The D-nucleosides 2,5,6-trichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8a) and 2-bromo-5,6-dichloro-1-(beta-D-erythrofuranosyl)benzimidazole (8b) were prepared by coupling 1,2,3,-tri-O-acetyl-beta-D-erythrofuranose (D-6) with the appropriate benzimidazole, followed by removal of the acetyl protecting groups. The 2-isopropylamino (9), 2-cyclopropylamino (10), and 2-mercaptobenzyl (11) derivatives were synthesized by nucleophilic displacements of the C-2 chlorine in the benzimidazole moiety of 8a. The D-nucleoside 4-bromo-5,6-dichloro-2-isopropylamino-1-(beta-D-erythrofuranosyl)benzimidazole (17) was prepared by coupling D-6 with the appropriate benzimidazole. The L-erythrofuranosyl derivatives, 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a), its 2-cyclopropylamine analogue (21b), and the 2-isopropylamino analogue (4c). In comparison, 8a was 15-fold more active against HCMV than 4a, and 8b was 4-fold more active against HCMV than 4b. The 5,6-dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimidazole (21a) was less active than 4c, which is now in clinical trials for HCMV infection. Both 8a,b had comparable HCMV activity to 4c. Mode of action studies with the D-erythrose analogues established that 8b acted by inhibition of viral DNA processing whereas 9 and 10 may act via a different mechanism. The lack of a 5'-hydroxymethyl group in all members of this series established that antiviral activity occurred without 5'-phosphorylation, a feature required for the activity of most nucleoside analogues.