9-(2-hydroxypropyl)guanine | 524018-84-6

• 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: 9-(2-hydroxypropyl)guanine
• 英文别名: 2-amino-9-(2-hydroxypropyl)-1H-purin-6-one
• CAS: 524018-84-6
• 化学式: C₈H₁₁N₅O₂
• 分子量: 209.208
• InChiKey: JRPUCMYAPJNJJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-(2-hydroxypropyl)guanine 在 Varicella-Zoster thymidine kinase 、 magnesium 、 5’-三磷酸腺苷 作用下， 以 水 为溶剂， 反应 1.0h， 生成 Phosphoric acid mono-[2-(2-amino-6-oxo-1,6-dihydro-purin-9-yl)-1-methyl-ethyl] ester
  参考文献：
  名称：

  Synthesis, Kinetics, and Molecular Docking of Novel 9-(2-Hydroxypropyl)purine Nucleoside Analogs as Ligands of Herpesviral Thymidine Kinases

  摘要：

  In the context of broadening the knowledge on substrate specificity of Herpes simplex virus type I thymidine kinase (HSV-1 TK) and Varicella-Zoster virus thymidine kinase (VZV TK), new derivatives of 9-(2-hydroxypropyl)-substituted adenine, chloropurine, hypoxanthine, guanine, thiopurine, and (methylsulfanyl)purine were synthesized and, subjected to in vitro phosphorylation and binding affinity assays. The interactions between the compounds and the crystallographically determined active site residues of HSV-1 TK have been studied by molecular modeling with the Lamarckian genetic algorithm of docking program AutoDock 3.0. All compounds mentioned bind to both enzymes in the low mm to sub-mM range, comparable to binding affinities of existing prodrugs. Findings from the docking procedure indicate multiple binding modes for all of the compounds and are in accordance with the results of phosphorylation and binding-affinity studies. Furthermore, the studies reveal that hypoxanthine derivatives represent a new class of TK substrates and thiopurine derivatives a new class of TK inhibitors.

  DOI：

  10.1002/1522-2675(200210)85:10<3237::aid-hlca3237>3.0.co;2-3
• 作为产物：
  描述：

  2-amino-6-chloro-9-(2-hydroxypropyl)-9H-purine 在 盐酸 作用下， 反应 2.0h， 以32%的产率得到9-(2-hydroxypropyl)guanine
  参考文献：
  名称：

  Synthesis, Kinetics, and Molecular Docking of Novel 9-(2-Hydroxypropyl)purine Nucleoside Analogs as Ligands of Herpesviral Thymidine Kinases

  摘要：

  In the context of broadening the knowledge on substrate specificity of Herpes simplex virus type I thymidine kinase (HSV-1 TK) and Varicella-Zoster virus thymidine kinase (VZV TK), new derivatives of 9-(2-hydroxypropyl)-substituted adenine, chloropurine, hypoxanthine, guanine, thiopurine, and (methylsulfanyl)purine were synthesized and, subjected to in vitro phosphorylation and binding affinity assays. The interactions between the compounds and the crystallographically determined active site residues of HSV-1 TK have been studied by molecular modeling with the Lamarckian genetic algorithm of docking program AutoDock 3.0. All compounds mentioned bind to both enzymes in the low mm to sub-mM range, comparable to binding affinities of existing prodrugs. Findings from the docking procedure indicate multiple binding modes for all of the compounds and are in accordance with the results of phosphorylation and binding-affinity studies. Furthermore, the studies reveal that hypoxanthine derivatives represent a new class of TK substrates and thiopurine derivatives a new class of TK inhibitors.

  DOI：

  10.1002/1522-2675(200210)85:10<3237::aid-hlca3237>3.0.co;2-3

文献信息

• [EN] ANTIRETROVIRAL ENANTIOMERIC NUCLEOTIDE ANALOGS<br/>[FR] ANALOGUES DE NUCLEOTIDES ENANTIOMERES ANTIRETROVIRAUX
  申请人：INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY OF THE ACADEMY OF SCIENCES OF THE CZECH REPUBLIC

  公开号：WO1994003467A2

  公开（公告）日：1994-02-17

  (EN) Resolved enantiomers of formulae (IA) and (IB) wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.(FR) Des énantiomères dédoublés des formules (IA) et (IB) où B est une base purique ou pyrimidique, ou bien des analogues aza et/ou désaza de ceux-ci sont utiles dans des compositions pharmaceutiques antivirales pour traiter des infections rétrovirales.

  (中文) 公式（IA）和（IB）的旋光异构体，其中B是嘌呤或嘧啶碱基或其氮杂环和/或去氮杂环衍生物，可用于抗病毒药物组合物中，用于治疗逆转录病毒感染。
• ANTIRETROVIRAL ENANTIOMERIC NUCLEOTIDE ANALOGS
  申请人：INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY OF THE ACADEMY OF SCIENCES OF THE CZECH REPUBLIC

  公开号：EP0654037A1

  公开（公告）日：1995-05-24
• US6057305A
  申请人：——

  公开号：US6057305A

  公开（公告）日：2000-05-02
• US6479673B1
  申请人：——

  公开号：US6479673B1

  公开（公告）日：2002-11-12
• US6653296B1
  申请人：——

  公开号：US6653296B1

  公开（公告）日：2003-11-25