9-(β-D-arabinofuranosyl)-6-azidopurine

• 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-azidopurine
• 英文别名: 9-(beta-D-Arabinofuranosyl)-6-azidopurine；(2R,3S,4S,5R)-2-(6-azidopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• 化学式: C₁₀H₁₁N₇O₄
• 分子量: 293.242
• InChiKey: RPEDALNTACVIFY-UHTZMRCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  阿糖腺苷 在 吡啶 、 氯化亚砜 、 叠氮化锂 、 氨 、 水 、 N,N-二甲基甲酰胺 、 adenosine deaminase 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 83.25h， 生成 9-(β-D-arabinofuranosyl)-6-azidopurine
  参考文献：
  名称：

  Synthesis, Biotransformation, and Pharmacokinetic Studies of 9-(β-d-Arabinofuranosyl)-6-azidopurine:  A Prodrug for Ara-A Designed To Utilize the Azide Reduction Pathway

  摘要：

  As a part of our efforts to design prodrugs for antiviral nucleosides, 9-(beta-4-arabinofuranosyl)-6-azidopurine (6-AAP) was synthesized as a prodrug for ara-A that utilizes the azide reduction biotransformation pathway. 6-AAP was synthesized from ara-A via its 6-chloro analogue 4. The bioconversion of the prodrug was investigated in vitro and in vivo, and the pharmacokinetic parameters were determined. For in vitro studies, 6-AAP was incubated in mouse serum and liver and brain homogenates. The half-lives of 6-AAP in serum and liver and brain homogenates were 3.73, 4.90, and 7.29 h, respectively. 6-AAP was metabolized primarily in the liver homogenate microsomal fraction by the reduction of the azido moiety to the amine, yielding ara-A. However, 6-AAP was found to be stable to adenosine deaminase in a separate in vitro study. The in vivo metabolism and disposition of ara-A and 6-AAP were conducted in mice. When 6-AAP was administered by either oral or intravenous route, the half-life of ara-A was 7-14 times higher than for ara-A administered intravenously. Ara-A could not be found in the brain after the intravenous administration of ara-A. However, after 6-AAP administration (by either oral or intravenous route), significant levels of ara-A were found in the brain. The results of this study demonstrate that 6-AAP is converted to ara-A, potentially increasing the half-life and the brain delivery of ara-A. Further studies to utilize the azide reduction approach on other clinically useful agents containing an amino group are in progress in our laboratories.

  DOI：

  10.1021/jm960339p

文献信息

• Therapeutic azide compounds
  申请人：University of Georgia Research Foundation, Inc.

  公开号：US20010036930A1

  公开（公告）日：2001-11-01

  Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

  提供了药物前药组成物，其中包括具有可在体内转化为药物的药物的偶氮衍生物。具有胺基，酮基和羟基取代基的药物的偶氮衍生物在体内转化为相应的药物，增加了药物的半衰期。此外，偶氮前药通常比相应的药物更能穿过血脑屏障。特别有用的是cordycepin，2'-F-ara-ddI，AraA，acyclovir，penciclovir和相关药物的偶氮衍生物。有用的偶氮前药是治疗性脂环烷胺，酮和羟基取代化合物的偶氮衍生物，包括芳基烷基，杂环芳基烷基和环状脂肪族化合物，其中胺基或氧原子基团位于环上，或胺基或氧原子基团位于脂肪侧链上，以及治疗性嘌呤和嘧啶，核苷类似物和磷酸化核苷类似物。
• Prodrug azide compositions and compounds
  申请人：University of Georgia Research Foundation Inc.

  公开号：US06271212B1

  公开（公告）日：2001-08-07

  Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

  提供药物前药组合物，其中包括能够在体内转化为药物的药物的叠氮化衍生物。具有胺基，酮基和羟基取代基的药物的叠氮化衍生物在体内转化为相应的药物，增加了药物的半衰期。此外，叠氮化前药通常比相应的药物更能穿透血脑屏障。特别有用的是cordycepin，2'-F-ara-ddI，AraA，acyclovir，penciclovir和相关药物的叠氮化衍生物。有用的叠氮化前药是治疗性脂环族胺，酮和羟基取代化合物的叠氮化衍生物，包括芳基烷基，杂环芳基烷基和环状脂肪族化合物，其中胺或氧基团位于环上，或胺或氧基团位于脂肪侧链上，以及治疗性嘌呤和嘧啶，核苷类似物和磷酸化核苷类似物的叠氮化衍生物。
• Compounds resistant to metabolic deactivation and methods of use
  申请人：Kane Ronald Robert

  公开号：US20060122144A1

  公开（公告）日：2006-06-08

  Therapeutic compounds having increased resistance to deamination and inactivation by metabolic enzymes are provided. The compounds include nucleotide analogs and nucleotide analogs, derivatized with aminal and/or thioaminal groups to prevent deamination of free amine. The compounds can be used in a variety of treatments, including treatment of neoplastic disorders, infections from fungal or fungal-like organisms, and infections from parasites.

  本研究提供了具有更强抗脱氨基能力和抗代谢酶失活能力的治疗化合物。 这些化合物包括核苷酸类似物和核苷酸类似物，用氨基和/或硫氨基衍生化，以防止游离胺的脱氨基作用。 这些化合物可用于多种治疗，包括治疗肿瘤性疾病、真菌或类真菌感染以及寄生虫感染。
• THERAPEUTIC AZIDE COMPOUNDS
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：EP0852499A1

  公开（公告）日：1998-07-15
• COMPOUNDS RESISTANT TO METABOLIC DEACTIVATION AND METHODS OF USE
  申请人：BAYLOR UNIVERSITY

  公开号：EP1581547A2

  公开（公告）日：2005-10-05