9-β-D-arabinofuranosyl-6-methoxy-9H-purine | 91969-06-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 9-β-D-arabinofuranosyl-6-methoxy-9H-purine
• 英文别名: 1-(6-methoxy-purin-9-yl)-β-D-1-deoxy-arabinofuranose；9-(β-D-Arabinofuranosyl)-6-methoxy-9H-purin；6-Methoxypurine arabinoside；(2R,3S,4S,5R)-2-(hydroxymethyl)-5-(6-methoxypurin-9-yl)oxolane-3,4-diol
• CAS: 91969-06-1
• 化学式: C₁₁H₁₄N₄O₅
• 分子量: 282.256
• InChiKey: UQQHOWKTDKKTHO-ICQCTTRCSA-N

物化性质

• 沸点：
  424.87°C (rough estimate)
• 密度：
  1.3304 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-β-D-arabinofuranosyl-6-methoxy-9H-purine 在 吡啶 作用下， 以 乙腈 为溶剂， 生成 Pentanoic acid (2R,3S,4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2-(6-methoxy-purin-9-yl)-4-pentanoyloxy-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  Di- and triester prodrugs of the varicella-zoster antiviral agent 6-methoxypurine arabinoside

  摘要：

  6-Methoxypurine arabinoside (9-beta-D-arabinofuranosyl-6-methoxy-9H-purine, 1) has potent and selective activity against varicella-zoster virus in vitro. An unfavorable metabolic profile observed with oral dosing in the rat led to the preparation of a variety of 2',3',5'-triesters (2a-n) and several 2',3'-, 2',5'-, and 3',5-diester, of this arabinoside (3a-n, 4a-f, and 5a-j, respectively). The compounds were evaluated as prodrugs by measuring the urinary levels of 1 in rat urine after oral dosing. With the exception of triacetate 2a, the triesters failed to significantly enhance bioavailability. Administration of compound 2a resulted in a 3-fold increase in systemic availability of 1, possibly because of its increased water solubility (1.6 times more soluble than 1) and only slightly increased relative log P value (1.93 vs 0.50 for 1). The longer chain aliphatic triesters and aromatic triesters had lower water solubilities and increased lipophilic partitioning. These factors might account for the lower systemic bioavailability of these compounds. In contrast, the diesters, especially the aliphatic diesters, showed significantly improved systemic availability. This might be a consequence of the higher aqueous solubilities and enhanced partition coefficients seen with these compounds. 2',3-Diacetate 3a showed the best combination of high systemic availability and water solubility of all the prodrugs of 1.

  DOI：

  10.1021/jm00079a006

文献信息

• Antiviral combinations and compounds therefor
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0349243A2

  公开（公告）日：1990-01-03

  The present invention relates to novel ribonucleotide reductase inhibitors and new combinations comprising of an antiviral compound, such as acyclovir, and a thiocarbonohydrazone ribonucleotide reductase inhibitor for the chemotherapeutic treatment or prophylaxis of virus infections, especially viruses of the herpes group.

  本发明涉及新型核糖核苷酸还原酶抑制剂以及由抗病毒化合物（如阿昔洛韦）和硫代甲酰腙核糖核苷酸还原酶抑制剂组成的新组合，用于病毒感染，特别是疱疹病毒的化学治疗或预防。
• Novel entities for cancer therapy
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0415731A2

  公开（公告）日：1991-03-06

  Novel molecular chimaeras produced by recombinant DNA techniques are described. They comprise a target tissue specific transcriptional regulatory sequence (TRS) linked and controlling the expression of a heterologous enzyme for example Varicella Zoster Virus Thymidine Kinase (VZV TK) gene. A molecular chimaera is packaged into a synthetic retroviral particle which is capable of infecting mammalian tissue. This in turn may be administered to a patient, and the TRS will be selectively transcriptionally activated in the target tissue (for example cancerous tissue). Administration of compounds which are selectively metabolised by the enzyme produce cytotoxic or cytostatic metabolites in situ thereby selectively killing or arresting the growth of the target cell.

  本文描述了通过 DNA 重组技术生产的新型分子嵌合体。它们包括一个目标组织特异性转录调控序列（TRS），该序列连接并控制异源酶的表达，例如水痘带状疱疹病毒胸苷激酶（VZV TK）基因。分子嵌合体被包装成能够感染哺乳动物组织的合成逆转录病毒颗粒。然后将其注射给病人，TRS 将在目标组织（例如癌组织）中被选择性地转录激活。施用经该酶选择性代谢的化合物，可在原位产生细胞毒性或细胞抑制性代谢产物，从而选择性地杀死或抑制靶细胞的生长。
• MOLECULAR CONSTRUCTS WITH A CARCINOEMBRYONIC ANTIGEN (CEA) TRANSCRIPTIONAL REGULATORY SEQUENCE
  申请人：——

  公开号：US20020055482A1

  公开（公告）日：2002-05-09

  Novel molecular chimaeras produced by recombinant DNA techniques are described. They comprise a target-tissue specific transcriptional regulatory sequence (TRS) linked and controlling the expression of a heterologous enzyme, for example Varicella Zoster Virus Thymidine Kinase (VZV TK) or non-mammaliam Cytosine Deaminase (CD). A molecular chimaera is packaged into a synthetic retroviral particle that is capable of infecting mammalian tissue. This, in turn, may be administered to a host, and the TRS will be selectively transcriptionally activated in the target tissue (for example cancerous cells). Administration of compounds that are selectively metabolised by the enzyme produce cytotoxic or cytostatic metabolites in situ thereby selectively killing or arresting the growth of the target cells.

  本文描述了通过 DNA 重组技术生产的新型分子嵌合体。它们包括一个目标组织特异性转录调控序列（TRS），该序列连接并控制着异源酶的表达，例如水痘带状疱疹病毒胸苷激酶（VZV TK）或非哺乳动物胞嘧啶脱氨酶（CD）。分子嵌合体被包装成能够感染哺乳动物组织的合成逆转录病毒颗粒。反过来，可将其施用给宿主，TRS 将在靶组织（例如癌细胞）中选择性地转录激活。施用被酶选择性代谢的化合物会在原位产生细胞毒性或细胞抑制性代谢产物，从而选择性地杀死或抑制靶细胞的生长。
• Antiviral compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0294114B1

  公开（公告）日：1996-09-11
• CHIMERIC TAR ENZYME CONSTRUCTION FOR HIV THERAPY
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0573479A1

  公开（公告）日：1993-12-15