arabinosyl 6-chloropurine | 7596-60-3

• 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: arabinosyl 6-chloropurine
• 英文别名: 9-(β-D-Arabinofuranosyl)-6-chloropurine；9-b-D-arabinofuranosyl-6-chloro-9H-Purine；(2R,3S,4S,5R)-2-(6-chloropurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 7596-60-3
• 化学式: C₁₀H₁₁ClN₄O₄
• 分子量: 286.675
• InChiKey: XHRJGHCQQPETRH-UHTZMRCNSA-N

物化性质

• 沸点：
  614.8±65.0 °C(Predicted)
• 密度：
  2.03

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  arabinosyl 6-chloropurine 在 叠氮化锂 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 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
• 作为产物：
  描述：

  阿糖腺苷 在 purine nucleoside 2’-deoxyribosyltransferase from Trypanosoma brucei 作用下， 以 aq. phosphate buffer 为溶剂， 反应 8.0h， 生成 arabinosyl 6-chloropurine
  参考文献：
  名称：

  使用来自布鲁氏锥虫的高度通用的嘌呤核苷2'-脱氧核糖基转移酶酶促合成治疗性核苷

  摘要：

  与多步化学方法相比，使用酶来合成核苷类似物具有多个优势，包括化学，区域和立体选择性以及较温和的反应条件。本文报道了来自布鲁氏锥虫的嘌呤核苷2'-脱氧核糖基转移酶（PDT）的生产，表征和利用。Tb PDT是一种二聚体，不仅在很宽的温度范围（50–70°C），pH（4–7）和离子强度（0–500 mM NaCl）范围内都显示出出色的活性和稳定性，而且在高温下具有非凡的高稳定性碱性条件（pH 8-10）。bPDT被证明可以熟练地合成许多治疗性核苷，包括去羟肌苷，维达拉滨，克拉屈滨，氟达拉滨和奈拉拉滨。用Ala或Ser进行结构指导的Val11置换，导致变体的活性提高了2.8倍。Tb PDT也共价固定在戊二醛激活的磁性微球上。选择了M Tb PDT3作为最佳衍生物（4200 IU / g，活性回收率为22％），可以轻松地将其重新捕获和再循环用于> 25个反应，而活性损失可忽略不计。最后，男铽PDT3

  DOI：

  10.1002/cctc.201800775

文献信息

• Synthesis and Antiviral Activity of 6-Chloropurine Arabinoside and Its 2'-Deoxy-2'-fluoro Derivative.
  作者：Tokumi MARUYAMA、Yoshiko SATO、Yuri OTO、Yuka TAKAHASHI、Robert SNOECK、Graciela ANDREI、Myriam WITVROUW、Eric De CLERCQ

  DOI：10.1248/cpb.44.2331

  日期：——

  6-Chloropurine arabinoside (3a) was obtained by treatment of the 2'-O-acetylated congener (2) with ammonia in methanol. The 3',5'-di-O-tritylated riboside (6) was allowed to react with diethylaminosulfur trifluoride (DAST) in the presence of pyridine to give the 2'-deoxy-2'-fluoroarabinoside (7), from which 6-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)purine (3b) was obtained. The antiviral

  通过用甲醇中的氨处理2'-O-乙酰化同源物（2），得到6-氯嘌呤阿拉伯糖苷（3a）。使3'，5'-二-O-三苯甲基化核糖苷（6）在吡啶存在下与二乙基氨基三氟化硫（DAST）反应，生成2'-脱氧-2'-氟阿拉伯糖苷（7），其中6获得-氯-9-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）嘌呤（3b）。测定了3a和3b对几种DNA和RNA病毒的抗病毒作用。只有3a显示出对水痘带状疱疹病毒（VZV）的有效活性。这种抗病毒活性取决于VZV诱导的胸苷激酶（TK）的磷酸化作用。化合物3a对其他DNA病毒，单纯疱疹1型（HSV-1）和2型（HSV-2）和牛痘病毒具有中等活性。它们对HSV-1的TK-和TK +菌株同样有效，这表明HSV-1编码的TK在抗HSV-1活性中不起作用。在低毒浓度下，任何化合物均未发现针对各种RNA病毒（包括人免疫缺陷病毒）的活性。
• 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。
• THERAPEUTIC AZIDE COMPOUNDS
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：EP0852499A1

  公开（公告）日：1998-07-15
• US6271212B1
  申请人：——

  公开号：US6271212B1

  公开（公告）日：2001-08-07
• [EN] THERAPEUTIC AZIDE COMPOUNDS<br/>[FR] COMPOSES AZIDES A USAGE THERAPEUTIQUE
  申请人：UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：WO1997009052A1

  公开（公告）日：1997-03-13

  (EN) Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug $i(in vivo). Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted $i(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.(FR) L'invention porte sur des compositions de promédicaments à usage pharmaceutique contenant des dérivés azides de médicaments, dérivés capables d'être convertis $i(in vivo) en médicament. Les dérivés azides de médicaments ayant des substituants amine, cétone et hydroxy sont convertis $i(in vivo) dans les médicaments correspondants, accroissant ainsi la demi-vie de ces médicaments. En outre, les promédicaments azides peuvent souvent pénétrer dans la barrière hémato-encéphalique mieux que les médicaments correspondants. Des dérivés azides particulièrement utiles sont constitués par des dérivés de cordydepine, de 2'-F-ara-ddI, d'AraA, d'acyclovir, de penciclovir et de médicaments associés. Des dérivés azides utiles sont constitués par des dérivés azides de composés substitués par amines, cétones et hydroxy, alicycliques et à usage thérapeutique, comprenant des composés aralkyles, aralkyles hétérocycliques et aliphatiques cycliques, la fraction d'amine ou d'oxygène se situant sur l'anneau ou sur une chaîne latérale aliphatique; et comprenant également des purines et des pyrimidines à usage thérapeutique, des analogues nucléosides et des analogues nucléosides phosphorylés.