6-tert-butyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine | 157891-99-1

• 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: 6-tert-butyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine
• 英文别名: 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-6-tert-butyl-5H-imidazo[1,2-a]purine；6-tert-butyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazo[1,2-a]purine；6-t-Bu-TRIC-ACV；6-t-Bu-TACV；6-tert-butyl-3-(2-hydroxyethoxymethyl)-5H-imidazo[1,2-a]purin-9-one
• CAS: 157891-99-1
• 化学式: C₁₄H₁₉N₅O₃
• 分子量: 305.337
• InChiKey: JHDQNNOPTORNCV-UHFFFAOYSA-N

物化性质

• 沸点：
  657.7±65.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  碘乙烷 、 6-tert-butyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以53%的产率得到6-t-butyl-3,9-dihydro-5-ethyl-3-[(2-hydroxyethoxy)methyl]-9-oxoimidazo[1,2-a]purine
  参考文献：
  名称：

  取代基-阿昔洛韦和鸟苷三环类似物的直接芳烷基化和烷基化反应

  摘要：

  摘要3,9-二氢-3-[（2-羟基乙氧基）甲基] -9-氧代-6-R-5H-咪唑并[1,2-α]嘌呤的6位上的芳基或叔丁基取代基（6 -R-TACV）1 1部分将芳烷基化反应引导到不同的位置：N-4生成3，C-7生成N-5，7-二取代或N-4，7-二取代的衍生物。在烷基化的情况下，该作用限于芳基取代基和位置N-4。用7中的核糖基取代1的无环部分可防止N-4取代。切割3b的第三个环以得到3-苄基阿昔洛韦10是制备3-芳烷基-9-取代的鸟嘌呤的新捷径的一个实例。

  DOI：

  10.1080/15257770008045468
• 作为产物：
  描述：

  阿昔洛韦 、 1-溴频哪酮 在 sodium hydride 作用下， 生成 6-tert-butyl-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

• A Convenient Approach to N-3 Alkylation of 9-Substituted Guanines
  作者：Tomasz Ostrowski、Joanna Zeidler、Tomasz Goelizski、Bozenna Golankiewicz

  DOI：10.1080/15257779908041495

  日期：1999.4

  Aryl or tert-butyl substituent in the 6 position of 3,9-dihydro-3-[(2-hydroxy-ethoxy)methyl]-9-oxo-6-R-5H-imid 1 directs the benzylation reaction partly into N-4 position to give 3. Cleavage of the third ring of 3 gives 3-benzylacycloguanosine 5, a first 3-aralkilo-9-substituted guanine.
• Substituent — Directed Aralkylation and Alkylation Reactions of the Tricyclic Analogues of Acyclovir and Guanosine
  作者：Tomasz Ostrowski、Joanna Zeidler、Tomasz Goslinski、Bozenna Golankiewicz

  DOI：10.1080/15257770008045468

  日期：2000.10

  Abstract Aryl or tert-butyl substituent in the 6 position of 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-6-R-5H-imidazo[1,2-α]purine (6-R-TACV)1 1 partly directs aralkylation reactions into unusual positions: N-4 to give 3 and C-7 to give N-5, 7-disubstituted or N-4, 7-disubstituted derivatives. In the case of alkylation the effect is limited to aryl substituent and position N-4. Replacement of acyclic

  摘要3,9-二氢-3-[（2-羟基乙氧基）甲基] -9-氧代-6-R-5H-咪唑并[1,2-α]嘌呤的6位上的芳基或叔丁基取代基（6 -R-TACV）1 1部分将芳烷基化反应引导到不同的位置：N-4生成3，C-7生成N-5，7-二取代或N-4，7-二取代的衍生物。在烷基化的情况下，该作用限于芳基取代基和位置N-4。用7中的核糖基取代1的无环部分可防止N-4取代。切割3b的第三个环以得到3-苄基阿昔洛韦10是制备3-芳烷基-9-取代的鸟嘌呤的新捷径的一个实例。
• 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.