2'-deoxy-4'-thioadenosine | 135656-35-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 2'-deoxy-4'-thioadenosine
• 英文别名: 4'-thio-2'-deoxyadenosine；(2R,3S,5R)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)thiolan-3-ol
• CAS: 135656-35-8
• 化学式: C₁₀H₁₃N₅O₂S
• 分子量: 267.312
• InChiKey: KSPWPIFRZGARDG-RRKCRQDMSA-N

物化性质

• 熔点：
  193-195 °C(Solv: ethanol (64-17-5))
• 沸点：
  630.5±65.0 °C(Predicted)
• 密度：
  1.92±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  18
• 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：
  135
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-deoxy-4'-thioadenosine 在 sodium periodate 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以98%的产率得到2'-deoxy-4'-thioadenosine S-Oxide
  参考文献：
  名称：

  作为 P2Y1 受体拮抗剂和部分激动剂的二磷酸核苷酸衍生物的构效关系。

  摘要：

  P2Y1 受体存在于心脏、骨骼和各种平滑肌以及血小板中，其激活与聚集有关。腺苷 3',5'- 和 2',5'-二磷酸已被鉴定为 P2Y1 受体的选择性拮抗剂 (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329)，并已进行结构修饰以增加受体亲和力（Camaioni 等 J. Med. Chem. 1998, 41, 183-190）。我们将结构-活性关系扩展到一系列新的脱氧腺苷二磷酸，并在腺嘌呤碱基、核糖部分和磷酸基团中进行了取代。通过测量其刺激火鸡红细胞膜中磷脂酶 C（激动剂作用）和抑制 10 nM 2-（甲硫基）腺苷 5'-二磷酸引起的磷脂酶 C 刺激（拮抗剂作用）的能力，确定每种类似物对 P2Y1 受体的活性。 。在腺嘌呤环的 2 位上含有卤素、氨基和硫醚基团的 2'-脱氧腺苷二磷酸类似物是比在 8 位上含有各种杂原子取代的类似物更有效的

  DOI：

  10.1021/jm980657j
• 作为产物：
  描述：

  N⁶-benzoyl-9-[2-bromo-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-β-D-arabinofuranosyl]adenine 在 偶氮二甲氧基异庚腈 、 四丁基氟化铵 、 三正丁基氢锡 、 溶剂黄146 、 甲胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 2'-deoxy-4'-thioadenosine
  参考文献：
  名称：

  Practical Synthesis of 2‘-Deoxy-4‘-thioribonucleosides:  Substrates for the Synthesis of 4‘-ThioDNA

  摘要：

  [GRAPHIC]We report herein a practical synthesis of 4'-thiothymidine (15) and appropriately protected 2'-deoxy-4'-thiocytidine (16), -thioadenosine (27), and -thioguanosine (29) derivatives, substrates for the synthesis of 4'-thioDNA, from the corresponding 4'-thioribonucleosides. 2'-Deoxy-4'-thiopyrimidine nucleosides were synthesized using a radical reaction of the corresponding 2'-alpha-bromo derivatives, which were prepared via 2,2'-O-anhydro derivatives. 2'-Deoxy-4'-thiopurine nucleosides were synthesized using the same radical reaction of the corresponding 2'-beta-bromo derivatives.

  DOI：

  10.1021/jo051248f

文献信息

• ALZHEIMER'S DISEASE THERAPEUTICS BASED ON PIN-1 CATALYZED CONFORMATIONAL CHANGES IN PHOSPHORYLATED AMYLOID PRECURSOR PROTEIN
  申请人：LU Ping Kun

  公开号：US20080058276A1

  公开（公告）日：2008-03-06

  The present invention is directed to inhibiting amyloidogenic processing of amyloid precursor protein, and/or inhibiting production of amyloid beta peptides. These methods can involve accelerating cis/trans isomerization of amyloid precursor protein at a phosphorylated serine/threonine-proline motif and/or contacting a cell with a compound that mimics the cis conformation of a phosphorylated serine/threonine-proline motif of an amyloid precursor protein. The present invention also relates to treating and/or preventing in a subject a degenerative neurological disease characterized by amyloidogenic processing of amyloid precursor protein and/or overproduction of amyloid beta peptide. This method involves administering an agent that accelerates cis/trans isomerization of amyloid precursor protein at a phosphorylated serine/threonine-proline motif and/or inhibits production of amyloid β peptides. Methods of screening for therapeutic agents effective in treating and/or preventing such diseases, methods of screening for biological molecules involved in the amyloidogenic pathway, and compounds that mimic the cis conformation of a phosphorylated serine/threonine-proline motif of an amyloid precursor protein are also disclosed.

  本发明旨在抑制淀粉样前体蛋白的淀粉样加工，并/或抑制淀粉样β肽的产生。这些方法可以涉及加速磷酸化丝氨酸/苏氨酸-脯氨酸基序的淀粉样前体蛋白的顺反异构化，和/或用类似于淀粉样前体蛋白磷酸化丝氨酸/苏氨酸-脯氨酸基序的顺式构象的化合物接触细胞。本发明还涉及用于治疗和/或预防患有淀粉样前体蛋白淀粉样加工和/或淀粉样β肽过度产生的退行性神经疾病的方法。该方法涉及给予一种能加速淀粉样前体蛋白磷酸化丝氨酸/苏氨酸-脯氨酸基序的顺反异构化和/或抑制淀粉样β肽产生的药物。还公开了筛选用于治疗和/或预防此类疾病的治疗剂的方法，筛选参与淀粉样加工途径的生物分子的方法，以及类似于淀粉样前体蛋白磷酸化丝氨酸/苏氨酸-脯氨酸基序的顺式构象的化合物。
• [EN] 2'-DEOXY-4'-THIORIBONUCLEOSIDES AS ANTIVIRAL AND ANTICANCER AGENTS
  申请人：SOUTHERN RESEARCH INSTITUTE

  公开号：WO1991004033A1

  公开（公告）日：1991-04-04

  (EN) 2'-Deoxy-4'-thio-ribonucleosides, intermediates in their production, and their use as antiviral and anticancer agents are disclosed.(FR) L'invention concerne des 2'-désoxy-4'-thio-ribonuclésides, des intermédiaires utilisés dans leur production, et leur utilisation en tant qu'agents antiviraux et anticancéreux.

  (EN) 2'-脱氧-4'-硫核苷酸，它们的中间产物以及作为抗病毒和抗癌药的用途得以披露。 (FR) L'invention concerne des 2'-désoxy-4'-thio-ribonuclésides, des intermédiaires utilisés dans leur production, et leur utilisation en tant qu'agents antiviraux et anticancéreux.
• Gene Therapy of Cancer: Activation of Nucleoside Prodrugs with<i>E. coli</i>Purine Nucleoside Phosphorylase
  作者：John A. Secrist、William B. Parker、Paula W. Allan、L. Lee Bennett、William R. Waud、Jackie W. Truss、Anita T. Fowler、John A. Montgomery、Steven E. Ealick、Alan H. Wells、G. Yancey Gillespie、V. K. Gadi、Eric J. Sorscher

  DOI：10.1080/15257779908041562

  日期：1999.4

  During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery off. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data.
• bis(<i>t</i>BuSATE) PHOSPHOTRIESTER PRODRUGS OF 8-AZAGUANOSINE AND 6-METHYLPURINE RIBOSIDE; bis(POM) PHOSPHOTRIESTER PRODRUGS OF 2′-DEOXY-4′-THIOADENOSINE AND ITS CORRESPONDING 9α ANOMER
  作者：J. D. Rose、W. B. Parker、J. A. Secrist

  DOI：10.1081/ncn-200061889

  日期：2005.4.1

  As an extension of previous work with bis(POM) nucleotide prodrugs, we report the synthesis and biological evaluation in tumor cell culture of the bis(pivaloyloxymethyl) phosphatriester prodrug of slightly cytotoxic 2'-deoxy-4'-thioadenosine and its alpha-anomer. We have experienced need for an alternative phosphate masking group, particularly with purine nucleosides. Accordingly, we report synthesis and biological evaluation of the bis(tBuSATE)phosphotriester prodrugs of 8-azaguanosine and 6-methylpurine riboside, nucleoside analogs with moderate to significant cytotoxicity. All four prodrugs were examined in tumor cell culture in parallel with the parent nucleosides. Synthetic routes and biological data are presented.
• EP0491793A4
  申请人：——

  公开号：EP0491793A4

  公开（公告）日：1993-03-03