3,9-dihydro-3-<(2-hydroxyethoxy)methyl>-9-oxo-6-phenyl-5H-imidazo<1,2-a>purine | 157892-00-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,9-dihydro-3-<(2-hydroxyethoxy)methyl>-9-oxo-6-phenyl-5H-imidazo<1,2-a>purine
• 英文别名: 6-phenyl-3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazol[1,2-a]purine；3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-6-phenyl-5H-imidazo[1,2-a]purine；6-Ph-TRIC-ACV；6-Ph-TACV；3-(2-hydroxyethoxymethyl)-6-phenyl-5H-imidazo[1,2-a]purin-9-one
• CAS: 157892-00-7
• 化学式: C₁₆H₁₅N₅O₃
• 分子量: 325.327
• InChiKey: HZPVMWKUUDHLAT-UHFFFAOYSA-N

物化性质

• 沸点：
  766.6±70.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  3,9-dihydro-3-<(2-hydroxyethoxy)methyl>-9-oxo-6-phenyl-5H-imidazo<1,2-a>purine 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 9-[(2-acetoxyethoxy)methyl]-N-2-acetyl-3-benzylguanine
  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 在 ammonium hydroxide 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3,9-dihydro-3-<(2-hydroxyethoxy)methyl>-9-oxo-6-phenyl-5H-imidazo<1,2-a>purine
  参考文献：
  名称：

  Fluorescent Tricyclic Analogues of Acyclovir and Ganciclovir. A Structure−Antiviral Activity Study

  摘要：

  Of a series of new guanine base modified tricyclic analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2), derivatives of the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system, evaluated for activity against herpes simplex virus type 1 and 2, several fluorescent analogues, 6-(4-MeOPli)-TACV (8), 7-Me-6-Ph-TACV (17), 6-(4-MeOPh)-TGCV (27), and 7-Me-6-Ph-TGCV (28), were obtained that showed similar potency and selectivity as the parent compounds. The activity was found to Le strongly dependent on the nature and steric demands of the substituents in the 6 and/or 7 position.

  DOI：

  10.1021/jm010922s

文献信息

• Fluorosubstitution and 7-alkylation as prospective modifications of biologically active 6-aryl derivatives of tricyclic acyclovir and ganciclovir analogues
  作者：Tomasz Ostrowski、Bozenna Golankiewicz、Erik De Clercq、Jan Balzarini

  DOI：10.1016/j.bmc.2005.01.004

  日期：2005.3

  A series of fluorine containing tricyclic analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) were synthesized and evaluated for their activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and cytostatic activity against HSV-1 thymidine kinase (TK) gene-transduced human osteosarcoma tumour cells. It was found that fluorine substitution reduced the antiviral activity, but most

  合成了一系列含氟的阿昔洛韦（ACV，1）和更昔洛韦（GCV，2）的三环类似物，并评估了它们对1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）的活性以及细胞抑制活性抗HSV-1胸苷激酶（TK）基因转导的人骨肉瘤肿瘤细胞。发现氟取代降低了抗病毒活性，但是大多数新化合物是明显的细胞抑制剂，其效力和选择性类似于亲本ACV和GCV。化合物12、13和16有望作为标记的底物用于HSV TK-配体相互作用的（19）F NMR研究和/或监测表达HSV TK的细胞中其代谢产物。
• 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.
• Unusual Tritylation Reactions of Tricyclic Analogues of Acyclovir and an Attempt to Elucidate Their Mechanism
  作者：Tomasz Goslinski、Joanna Zeidler、Bozenna Golankiewicz

  DOI：10.1002/(sici)1522-2675(20000216)83:2<373::aid-hlca373>3.0.co;2-n

  日期：2000.2.16

  In reference to our earlier observation that the 3,9-dihydro-3-[ (2-hydroxyethoxy)methyl]-6-methyl-9-oxo-5H-imidazo[1,2-a]purine (6-Me-TACV) tricyclic antiviral agent derived from acyclovir undergoes unusual C-tritylation to 7-trityl and 7-[4-(benzhydryl)phenyl] derivatives enforced by a 6-Mc substituent, we studied tritylation of 6-Ph (1a) and 6-(4-MeOPh) (1b) TACV derivatives. The treatment of 1a and 1b with TrCl in K2CO3/DMF resulted exclusively in the formation of 7-[4-(benzhydryl)phenyl] derivatives 2a, 2b, 3a, 3b, and 4a. inhibition experiments with radical scavengers DNB and DBNO indicated a single-electron-transfer (SET) mechanism for this reaction. Analogous experiments with unsubstituted TACV and 6-Me-TACV suggest that the nature of the substituent at C(6) determines the reaction mechanism. The presence of a 6-aryl substituent results in the exclusive formation of 4-(benzhydryl)phenyl derivatives via a SET mechanism. On the contrary, when C(6) is unsubstituted, trityl derivatives are the only products of the S-N reaction. In the case of 6-Me-TACV, concomitant SET and S-N mechanisms direct the reaction towards 4-(benzhydryl)phenyl and trityl products.
• 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。