3-(2-羟基乙氧基甲基)-6-甲基-5H-咪唑并[1,2-a]嘌呤-9-酮 | 114199-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 3-(2-羟基乙氧基甲基)-6-甲基-5H-咪唑并[1,2-a]嘌呤-9-酮
• 英文名称: 6-methyl-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]-6-methyl-9-oxo-5H-imidazo[1,2-a]purine；3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-6-methyl-5H-imidazo[1,2-a]purine；6-methyl-TRIC-ACV；9-[(2-Hydroxyethoxy)methyl]-1,N-2-(prop-1-ene-1,2-diyl)guanine；3,9-Dihydro-3-((2-hydroxyethoxy)methyl)-6-methyl-9-oxo-5H-imidazo(1,2-a)purine；3-(2-hydroxyethoxymethyl)-6-methyl-5H-imidazo[1,2-a]purin-9-one
• CAS: 114199-19-8
• 化学式: C₁₁H₁₃N₅O₃
• 分子量: 263.256
• InChiKey: IKOQPTHMJTZXDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  19
• 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

• 作为反应物：
  描述：

  3-(2-羟基乙氧基甲基)-6-甲基-5H-咪唑并[1,2-a]嘌呤-9-酮 在 ammonium hydroxide 、 碘 作用下， 以 甲醇 为溶剂， 生成 阿昔洛韦
  参考文献：
  名称：

  Boryski, Jerzy; Ostrowski, Tomasz; Baranowski, Daniel, Collection of Czechoslovak Chemical Communications, 1996, vol. 61, p. S38 - S41

  摘要：

  DOI：
• 作为产物：
  描述：

  阿昔洛韦 、 溴丙酮 在 ammonium hydroxide 、 sodium hydride 作用下， 生成 3-(2-羟基乙氧基甲基)-6-甲基-5H-咪唑并[1,2-a]嘌呤-9-酮
  参考文献：
  名称：

  Synthesis and antiviral activity of novel N-substituted derivatives of acyclovir

  摘要：

  Novel N-substituted derivatives of acyclovir (1a) were synthesized and evaluated for their antiviral, antimetabolic, and antitumor cell properties in vitro. Monomethylation of 1a at positions 1, 7, and N-2 gave compounds 2-4, respectively. When positions 1 and N-2 were linked together by an isopropeno group, the tricyclic 9-[(2-hydroxyethoxy)methyl]-1,N-2-isopropenoguanine (5) was obtained. Compound 5 was then further methylated at positions N-2 and 7 to give 6 and 7, respectively. None of the new acyclovir derivatives showed any appreciable antimetabolic or antitumor cell activity. However, compounds 2 and 5 exhibited a marked antiherpetic activity. Their activity spectrum was similar to that of acyclovir, and their selectivity as inhibitors of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was at least as great as, if not greater than, that of acyclovir.

  DOI：

  10.1021/jm00402a017

文献信息

• 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。
• Golankiewicz, Bozenna; Ostrowski, Tomasz; Boryski, Jerzy, Journal of the Chemical Society. Perkin transactions I, 1991, # 3, p. 589 - 593
  作者：Golankiewicz, Bozenna、Ostrowski, Tomasz、Boryski, Jerzy、Clercq, Erik De

  DOI：——

  日期：——
• A case of unusual sterically driven C-tritylation reaction of tricyclic analogues of acyclovir
  作者：Joanna Zeidler、Bożenna Golankiewicz

  DOI：10.1016/s0040-4020(98)83029-9

  日期：1998.3

  3,9-Dihydro-3-[(2-hydroxyethoxy)methyl] 6-methyl-9-oxo-5H-imidazo[1,2-a]purine (1) and its silylated derivative (2) when tritylated under conditions suitable for regioselective N-5 alkylation underwent instead C-substitution to give 7-trityl (12, 3) and 7-(4-benzhydrylphenyl) (13, 4) derivatives as major and minor products, respectively. Substrates lacking 6-Me group (5, 6) yielded 5-tritylated (10, 7) and 5,7-ditritylated (11, 8) major products and 7-tritylated (9) minor product. The regioselectivity of the reaction seems to be driven mainly by steric hindrance of the 6-Me substituent. (C) 1998 Elsevier Science Ltd. All rights reserved.
• 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.