2-bromo-6-methyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-bromo-6-methyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine
• 英文别名: 2-Br-6-Me-TRIC-ACV；2-Br-6-Me-TACV；2-bromo-3-(2-hydroxyethoxymethyl)-6-methyl-5H-imidazo[1,2-a]purin-9-one
• 化学式: C₁₁H₁₂BrN₅O₃
• 分子量: 342.152
• InChiKey: AGASSTHGGSUOOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-bromoacyclovir 、 溴丙酮 在 sodium hydride 作用下， 生成 2-bromo-6-methyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine
  参考文献：
  名称：

  Tricyclic Analogs of Acyclovir and Ganciclovir. Influence of Substituents in the Heterocyclic Moiety on the Antiviral Activity

  摘要：

  The effect of substitution in the tricyclic moiety of 3,9-dihydro-9-oxo-5H-imidazo[1,2-alpha]purine (1,N-2-ethenoguanine) analogues of acyclovir (1) and ganciclovir (2) on their physical properties and antiherpetic activity was investigated by synthesizing a series of compounds substituted in the 2, 6, or 7 position (6-14). Substitution in the 6-position with phenyl or 4-biphenylyl resulted in fluorescent compounds (7, 9, 13, 14). In general, the substituent in the 6 position potentiated the antiviral activity. The fluorescent 6-phenyl derivatives: 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-6-phenyl- 5H-imidazo[1,2-alpha]purine (7) and its 3-[( 1,3-dihydroxy-2-propoxy)methyl] congener (13) were the most potent tricyclic analogues of 1 and 2, respectively. Compound 7 was inhibitory to TK+ HSV-1, TK+ HSV-2, and TK+ VZV within the concentration range of 0.2-2.0 mu g/mL, well below the cytotoxicity threshold (50 to > 100 mu g/mL). Compound 13 was inhibitory to TK+ HSV-1 and TK+ HSV-2 within the concentration range of 0.005-0.3 mu g/mL and to TK+ and TK- VZV within the concentration range of 0.4-3 mu g/mL (cytotoxicity threshold > 200 mu g/mL). Both 7 and 13 seem to be promising candidate compounds for the noninvasive diagnosis of herpesvirus infections.

  DOI：

  10.1021/jm00045a025

文献信息

• Tricyclic Analogs of Acyclovir and Ganciclovir. Influence of Substituents in the Heterocyclic Moiety on the Antiviral Activity
  作者：Bozenna Golankiewicz、Tomasz Ostrowski、Graciela Andrei、Robert Snoeck、Erik De Clercq

  DOI：10.1021/jm00045a025

  日期：1994.9

  The effect of substitution in the tricyclic moiety of 3,9-dihydro-9-oxo-5H-imidazo[1,2-alpha]purine (1,N-2-ethenoguanine) analogues of acyclovir (1) and ganciclovir (2) on their physical properties and antiherpetic activity was investigated by synthesizing a series of compounds substituted in the 2, 6, or 7 position (6-14). Substitution in the 6-position with phenyl or 4-biphenylyl resulted in fluorescent compounds (7, 9, 13, 14). In general, the substituent in the 6 position potentiated the antiviral activity. The fluorescent 6-phenyl derivatives: 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-6-phenyl- 5H-imidazo[1,2-alpha]purine (7) and its 3-[( 1,3-dihydroxy-2-propoxy)methyl] congener (13) were the most potent tricyclic analogues of 1 and 2, respectively. Compound 7 was inhibitory to TK+ HSV-1, TK+ HSV-2, and TK+ VZV within the concentration range of 0.2-2.0 mu g/mL, well below the cytotoxicity threshold (50 to > 100 mu g/mL). Compound 13 was inhibitory to TK+ HSV-1 and TK+ HSV-2 within the concentration range of 0.005-0.3 mu g/mL and to TK+ and TK- VZV within the concentration range of 0.4-3 mu g/mL (cytotoxicity threshold > 200 mu g/mL). Both 7 and 13 seem to be promising candidate compounds for the noninvasive diagnosis of herpesvirus infections.