2-bromo-5,6-dichloro-1-(2,3-di-O-acetyl-β-D-erythrofuranosyl)benzimidazole | 286942-13-0

• 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-bromo-5,6-dichloro-1-(2,3-di-O-acetyl-β-D-erythrofuranosyl)benzimidazole
• 英文别名: [(3R,4R,5R)-4-acetoxy-5-(2-bromo-5,6-dichloro-benzimidazol-1-yl)tetrahydrofuran-3-yl] acetate；[(3R,4R,5R)-4-acetyloxy-5-(2-bromo-5,6-dichlorobenzimidazol-1-yl)oxolan-3-yl] acetate
• CAS: 286942-13-0
• 化学式: C₁₅H₁₃BrCl₂N₂O₅
• 分子量: 452.089
• InChiKey: GTVHXHHTVLNHNP-MGPQQGTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  79.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-bromo-5,6-dichloro-1-(2,3-di-O-acetyl-β-D-erythrofuranosyl)benzimidazole 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以85%的产率得到2-bromo-5,6-dichloro-1-(β-D-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：

  2-溴-5,6-二氯-1H-苯并咪唑 在 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 2.33h， 生成 2-bromo-5,6-dichloro-1-(2,3-di-O-acetyl-β-D-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

文献信息

• 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.