9-<5-Deoxy-5(Z)-fluoro-β-D-erythro-pent-4-enofuranosyl>adenine | 119244-37-0

• 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-<5-Deoxy-5(Z)-fluoro-β-D-erythro-pent-4-enofuranosyl>adenine
• 英文别名: (Z)-9-(5-deoxy-5-fluoro-β-D-erythro-pent-4-enofuranosyl)adenine；(Z)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine；(2R,3R,4S,5Z)-2-(6-aminopurin-9-yl)-5-(fluoromethylidene)oxolane-3,4-diol
• CAS: 119244-37-0
• 化学式: C₁₀H₁₀FN₅O₃
• 分子量: 267.22
• InChiKey: NAWIFPQLACUTSO-QCUWZOMOSA-N

物化性质

• 熔点：
  218-221 °C
• 沸点：
  577.7±60.0 °C(Predicted)
• 密度：
  1.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-<5-Deoxy-5(Z)-fluoro-β-D-erythro-pent-4-enofuranosyl>adenine 在 phosphate buffer 作用下， 反应 3.0h， 以87%的产率得到(4'Z)-4',5'-Didehydro-5'-deoxy-5'-fluoroinosine
  参考文献：
  名称：

  AMP Deaminase as a Novel Practical Catalyst in the Synthesis of 6-Oxopurine Ribosides and their Analogs

  摘要：

  Adenylic acid deaminase from Aspergillus niger (AMP deaminase; AMPDA; EC 3.5.4.6) has been introduced as a novel practical catalyst in the synthesis of 6-oxopurine riboside and their analogs. This enzyme has a very broad substrate specificity and has been used on a preparative scale for deamination of several derivatives of adenosine including phosphorylated, cyclic, carbocyclic as well as acyclic analogs. In addition, AMPDA catalyzes dechlorination and demethoxylation of the purine ribosides. Overall substrate specificity of AMPDA is much broader than that of adenosine deaminase which can also be used for the synthesis of 6-oxopurine ribosides. Although the stereoselectivity of AMPDA is modest, this enzyme has successfully been used in the synthesis of a novel antiviral agent, carbovir phosphonate (14), after the carbocyclic component was resolved via lipase-catalyzed hydrolysis or acylation.

  DOI：

  10.1021/jo00103a010
• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 二乙胺基三氟化硫 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 甲醇 、 丙酮 为溶剂， 生成 9-<5-Deoxy-5(Z)-fluoro-β-D-erythro-pent-4-enofuranosyl>adenine
  参考文献：
  名称：

  4',5'-Unsaturated-5'-fluoro adenosine nucleosides: potent mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase

  摘要：

  DOI：

  10.1021/ja00185a052

文献信息

• 4'-5'-Unsaturated 5'-halogenated nucleosides. Mechanism-based and competitive inhibitors of S-adenosyl-L-homocysteine hydrolase
  作者：Esa T. Jarvi、James R. McCarthy、Shujaath Mehdi、Donald P. Matthews、Michael L. Edwards、Nellikunja J. Prakash、Terry L. Bowlin、Prasad S. Sunkara、Philippe Bey

  DOI：10.1021/jm00106a028

  日期：1991.2

  an extra chlorine to the 5'-vinyl position (i.e. 51 and 52), modification of the 2'-hydroxyl group to the deoxy (34 and 35) and arabino (36 and 37) nucleosides provided competitive inhibitors of SAH hydrolase. Nucleosides 6 and 13, as well as 5'-deoxy-5',5'-difluoroadenosine (14) proved to be time-dependent inhibitors of SAH hydrolase. All three compounds are postulated to inhibit through the potent

  （E）-和（Z）-5'-氟-4'，5'-二氢-5'-脱氧腺苷（分别为6和13）的设计和合成，这是一类新的基于机理的S-抑制剂描述了腺苷-L-高半胱氨酸（SAH）水解酶。为了确定抑制该酶所必需的结构-活性关系，合成了许多6和13的类似物。用氯代替6（即44）中的氟，在5'-乙烯基位置（即51和52）添加额外的氯，将2'-羟基修饰为脱氧（34和35）和阿拉伯糖（ 36和37）核苷提供了SAH水解酶的竞争性抑制剂。核苷6和13以及5'-脱氧-5'，5'-二氟腺苷（14）被证明是SAH水解酶的时间依赖性抑制剂。假定所有这三种化合物都通过强力亲电试剂来抑制，该亲电试剂是由6或13的3'-羟基氧化成酮（即3和/或E-异构体）而形成的。与提出的通过6、13和14灭活SAH水解酶的机理一致的观察结果是，纯化的大鼠肝脏SAH水解酶与6孵育会释放1当量的氟离子（通过19F NMR），与14孵育会导致释放2当量
• 5'-vinylhalo-aristeromycin/adenosine analogs and immunosuppressants
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05470837A1

  公开（公告）日：1995-11-28

  The present invention relates to a method of effecting immunosuppression in a patient in need thereof comprising administering to said patient an effective immunosuppressive amount of certain 5'-vinylhalo-aristeromycin/adenosine analogs.

  本发明涉及一种在需要免疫抑制的患者中施用一定量的有效免疫抑制剂5'-乙烯基卤代阿立哌唑/腺苷类似物的方法。
• 5'-deoxy-4',5'-unsaturated-5'-substituted adenosines
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US04997924A1

  公开（公告）日：1991-03-05

  This invention relates to certain aristeromycin/adenosine derivatives which are useful in inhibiting AdoMet-dependent transmethylation and in the treatment of patients afflicted with neoplastic or viral disease states.

  本发明涉及某些阿里斯特罗霉素/腺苷衍生物，可用于抑制AdoMet依赖性转甲基化并用于治疗患有肿瘤或病毒性疾病状态的患者。
• Aristeromycin analogues of 4',5'-didehydro-5'-fluoro-adenosine and
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05521162A1

  公开（公告）日：1996-05-28

  This invention relates to certain aristeromycin/adenosine derivatives which are useful in inhibiting AdoMet-dependent transmethylation and in the treatment of patients afflicted with neoplastic or viral disease states.

  本发明涉及某些左旋核苷酸/腺苷酸衍生物，其在抑制AdoMet依赖性转甲基化和治疗患有肿瘤或病毒性疾病状态的患者方面具有用途。
• Novel aristeromycin/adenosine derivatives
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0304889A2

  公开（公告）日：1989-03-01

  This invention relates to certain aristeromycin/adenosine derivatives which are useful in inhibiting AdoMet-dependent transmethylation and in the treatment of patients afflicted with neoplastic or viral disease states.

  本发明涉及某些阿里斯托霉素/腺苷衍生物，这些衍生物可用于抑制 AdoMet 依赖性转甲基化和治疗肿瘤性或病毒性疾病患者。