5'-S-(4-methoxyphenyl)-5'-thioadenosine | 137103-06-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-S-(4-methoxyphenyl)-5'-thioadenosine
• 英文别名: (2R,3R,4S,5S)-2-(6-Amino-9H-purin-9-yl)-5-(((4-methoxyphenyl)thio)methyl)tetrahydrofuran-3,4-diol；(2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-[(4-methoxyphenyl)sulfanylmethyl]oxolane-3,4-diol
• CAS: 137103-06-1
• 化学式: C₁₇H₁₉N₅O₄S
• 分子量: 389.435
• InChiKey: YPBFMIZDPCDUOG-LSCFUAHRSA-N

物化性质

• 沸点：
  722.1±70.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-S-(4-methoxyphenyl)-5'-thioadenosine 在 吡啶 、 二氟代氙 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 生成 (5'S)-2',3'-Di-O-acetyl-5'-fluoro-5'-S-(4-methoxyphenyl)-5'-thioadenosine
  参考文献：
  名称：

  Nucleic Acid Related Compounds. 80. Synthesis of 5'-S-(Alkyl and aryl)-5'-fluoro-5'-thioadenosines with Xenon Difluoride or (Diethylamido)sulfur Trifluoride, Hydrolysis in Aqueous Buffer, and Inhibition of S-Adenosyl-L-homocysteine hydrolase by derived "Adenosine 5'-Aldehyde" Species

  摘要：

  Treatment of 5/-S-(alkyl and aryl)-5'-thioadenosine derivatives 2 with XeF2, or the corresponding sulfoxides 3 with DAST/SbCl3, gave diastereomeric 5'-fluoro compounds which were deprotected to give the 5'-S-(alkyl and aryl)-5'-fluoro-5'-thioadenosine analogues 5. Stereochemistry was established by X-ray crystallography, and F-19 NMR chemical shifts were definitive for configurationally-related 5'-fluoro diastereomers. Sulfoxidation and thermolysis afforded the fluoromethylene analogues with retained relative configuration. The nucleoside 5'-alpha-fluoro thioethers 5 underwent spontaneous hydrolysis in aqueous buffer to give derived ''adenosine 5'-aldehyde'' species which caused potent time-dependent inactivation of S-adenosyl-L-homocysteine hydrolase.

  DOI：

  10.1021/jo00082a010
• 作为产物：
  描述：

  5'-chloro-5'-deoxy-2',3'-O-sulphinyladenosine hydrochloride 在 ammonium hydroxide 、 sodium hydride 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 5'-S-(4-methoxyphenyl)-5'-thioadenosine
  参考文献：
  名称：

  Nucleic acid related compounds. 66. Improved syntheses of 5′-chloro-5′-deoxy- and 5′-S-aryl(or alkyl)-5′-thionucleosides

  摘要：

  使用硫酰氯/吡啶/乙腈（0°C至室温）处理核糖核苷可基本定量形成5'-氯-5'-脱氧-2'，3'-O-亚磺酰核苷衍生物。这些对映异构的亚硫酸酯酯可以轻松地通过甲醇氨水溶液去保护基。这样就可以不使用疑似致癌物六甲基磷酰胺（HMPA）制备5'-氯-5'-脱氧核苷。在二甲基甲酰胺中，通过钠硫醇的亲核置换反应（-30°C至室温），可以高产得到5'-S-芳基（或烷基）-5'-硫代核苷。使用硫酰氯/乙腈而不是吡啶处理核糖核苷，然后进行水处理，可以得到未修饰的5'-羟基核苷的对映异构的2'，3'-O-亚磺酰核苷。文中还提到了环状亚硫酸酯立体化学的诊断NMR位移。关键词：腺苷，5'-S-芳基（或烷基）-5'-硫代核苷，5'-氯-5'-脱氧核苷，尿苷，核苷。

  DOI：

  10.1139/v91-217

文献信息

• Combination therapies for treating methylthioadenosine phosphorylase deficient cells
  申请人：——

  公开号：US20040043959A1

  公开（公告）日：2004-03-04

  The present invention is directed to combination therapies for treating cell proliferative disorders associated with methylthioadenosine phosphorylase (MTAP) deficient cells in a mammal. The combination therapies selectively kill MTAP-deficient cells by administering an inhibitor of de novo inosinate synthesis and administering an anti-toxicity agent, wherein the inhibitors of de novo inosinate synthesis are inhibitors of glycinamide ribonucleotide formyltransferase (“GARFT”) and/or aminoinidazolecarboximide ribonucleotide formyltransferase (“AICARFT”), and the anti-toxicity agent is an MTAP substrate (e.g. methylthioadenosine or “MTA”), a precursor of MTA, an analog of an MTA precursor or a prodrug of an MTAP substrate.

  本发明涉及用于治疗哺乳动物中与甲基硫腺苷磷酸化酶（MTAP）缺乏细胞相关的细胞增殖性疾病的联合疗法。该联合疗法通过给予新生核苷酸合成抑制剂和给予抗毒性剂，选择性地杀死MTAP缺乏细胞，其中，新生核苷酸合成抑制剂是甘氨酰核苷酸甲酰转移酶（“GARFT”）和/或氨基咪唑羧酰核苷酸甲酰转移酶（“AICARFT”）的抑制剂，抗毒性剂是MTAP底物（例如，甲基硫腺苷或“MTA”），MTA的前体，MTA前体的类似物或MTAP底物的前药。
• Design, synthesis, and biological evaluation of novel human 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP) substrates
  作者：Pei-Pei Kung、Luke R. Zehnder、Jerry J. Meng、Stanley W. Kupchinsky、Donald J. Skalitzky、M. Catherine Johnson、Karen A. Maegley、Anne Ekker、Leslie A. Kuhn、Peter W. Rose、Laura A. Bloom

  DOI：10.1016/j.bmcl.2005.03.107

  日期：2005.6

  The structure-based design, chemical synthesis, and biological evaluation of novel MTAP substrates are described. These compounds incorporate various C5'-moieties and are shown to have different k(cat)/K values compared with the natural MTAP substrate (MTA). (c) 2005 Elsevier Ltd. All rights reserved.
• Fluorination at C5′ of nucleosides. Synthesis of the new class of 5′-fluoro-5′-S-aryl (alkyl) thionucleosides from adenosine.
  作者：Morris J. Robins、Wnuk F. Stanislaw

  DOI：10.1016/s0040-4039(00)82174-7

  日期：1988.1
• Nucleic Acid Related Compounds. 82. Conversions of Adenosine to Inosine 5′-Thioether Derivatives with<i>Aspergillus oryzae</i>Adenosine Deaminase or Alkyl Nitrites. Substrate and Inhibitory Activities of Inosine 5′-Thioether Derivatives with Purine Nucleoside Phosphorylase
  作者：Stanislaw F. Wnuk、Johanna D. Stoeckler、Morris J. Robins

  DOI：10.1080/15257779408013249

  日期：1994.3

  Adenosine derivatives lacking a 5'-hydroxyl group seldom act as alternative substrates of adenosine deaminases from calf intestine and other mammalian sources. A deaminase from Aspergillus oryzae deaminated adenosine 5'-thioether derivatives cleanly and more efficiently than alkyl nitrites. The inosine derivatives were very poor alternative substrates and weak inhibitors of purine nucleoside phosphorylase.
• Nucleic acid related compounds. 76. Synthesis of 5'(E and Z)-chloro-4',5'-didehydro-5'-deoxyadenosines via chlorination and thermolysis of adenosine 5'-sulfoxides. Mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase
  作者：Stanislaw F. Wnuk、N. Kent Dalley、Morris J. Robins

  DOI：10.1021/jo00053a022

  日期：1993.1

  Treatment of 2',3'-di-O-acetyl-5'-S-(4-methoxyphenyl)-5'-thioadenosine (1a), or its sulfoxides 2a(S(R)) and 3a(S(S)), with iodobenzene dichloride and potassium carbonate in acetonitrile resulted in formation of the 5'-chloro(and 5',5'-dichloro)-5'-deoxy-5'-[(4-methoxyphenyl)sulfinyl]adenosines 4a, 5a, 6a, and minor diastereomers. Deprotection of 5a gave 5'(S)-chloro-5'-deoxy-5'-[(4-methoxyphenyl)-sulfinyl(S(S))]adenosine [5b(5'S,S(S))] whose stereochemistry and conformation were established by X-ray crystallography. The alpha-chlorination of sulfoxides 2a(S(R)) and 3a (S(S)) occurred with predominant retention of configuration at sulfur. Thermolysis of the alpha-chloro sulfoxides and deprotection gave the chloromethylene derivatives. The 5'(Z)-chloro-4',5'-didehydro-5'-deoxyadenosine [9b(5'Z)] diastereomer was found to be a potent time-dependent inhibitor of S-adenosyl-L-homocysteine hydrolase.