5'-acetylthio-5'-deoxyadenosine | 139361-69-6

• 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'-acetylthio-5'-deoxyadenosine
• 英文别名: 5′-thioacetyladenosine；5'-acetylthioadenosine；5'-thioadenosine；5'-deoxy-5'-acetyl-thioadenosine；S-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl] ethanethioate
• CAS: 139361-69-6
• 化学式: C₁₂H₁₅N₅O₄S
• 分子量: 325.348
• InChiKey: ZAOSQJHLUDMSTB-WOUKDFQISA-N

物化性质

• 沸点：
  665.9±65.0 °C(Predicted)
• 密度：
  1.87±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-acetylthio-5'-deoxyadenosine 在 氨 作用下， 以 甲醇 为溶剂， 以90%的产率得到5'-硫代腺苷
  参考文献：
  名称：

  用新型5'-硫代腺苷衍生物灭活S-腺苷-L-高半胱氨酸水解酶。抗病毒作用。

  摘要：

  描述了5'-S-乙烯基-5'-硫代腺苷5、5'-S-乙炔基-5'-硫代腺苷7和5'-S-氰基-5'-硫代腺苷9的合成。用5、7和9孵育AdoHcy水解酶会导致该酶的时间和浓度依赖性失活以及其NAD（+）含量的部分消耗。从这些结果和灭活过程中释放的代谢产物的特征，提出了推测的机制。检查了5、7和9的抗病毒活性。注意到有5种针对牛痘，胡宁和牛痘病毒的显着活性。

  DOI：

  10.1016/s0960-894x(03)00279-8
• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 甲酸 、 水 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 45.0h， 生成 5'-acetylthio-5'-deoxyadenosine
  参考文献：
  名称：

  S-腺苷-L-高半胱氨酸天然产物类似物的有效合成及其在阐明 DNA 甲基转移酶 M·HhaI 辅因子结合的结构决定因素中的应用

  摘要：

  5'-Acetylthio-5'-deoxy-2',3'-O-isopropylideneadenosine (8) 由市售的 2',3'-O-isopropylideneadenosine (7) 和硫代乙酸在 Mitsunobu 条件下以几乎定量的产率直接制备. 原位裂解 8 的乙酰硫基官能团，然后与不同的烷基溴进行偶联，收率很高。获得的 5'-硫代核苷的脱保护产生 S-腺苷-L-高半胱氨酸类似物脱羧的 AdoHcy (11)、脱氨基的 AdoHcy (14) 和 5'-[3-(氰基)丙硫基]-5'-脱氧腺苷 (16)良好的整体收益率。硫代核苷 8 的直接脱保护以优异的产率提供 5'-thio-5'-deoxyadenosine (18)。此外，这些 AdoHcy 类似物和 DNA 甲基转移酶 M·HhaI 的结合常数在荧光测定中确定。

  DOI：

  10.1002/(sici)1099-0690(200002)2000:3<549::aid-ejoc549>3.0.co;2-7

文献信息

• Method for Identifying Inhibitors Using a Homology Model of Polo-Like Kinase 1
  申请人：McInnes Campbell

  公开号：US20080132484A1

  公开（公告）日：2008-06-05

  The present invention relates to a homology model for PLK, and the use thereof in assays for the identification of small molecule PLK modulators. The invention further relates to PLK modulators identified by said assays, and their use in the treatment of PLK-related disorders such as proliferative disorders.

  本发明涉及一种用于PLK的同源模型，以及其在用于鉴定小分子PLK调节剂的测定中的应用。该发明还涉及通过上述测定鉴定出的PLK调节剂，以及它们在治疗与PLK相关的增生性疾病等疾病中的应用。
• Synthesis of Adenine Dinucleosides 2′,5′-Bridged by Sulfur-Containing Linkers as Bisubstrate SAM Analogues for Viral RNA 2′-<i>O</i> -Methyltransferases
  作者：Rostom Ahmed-Belkacem、Priscila Sutto-Ortiz、Etienne Decroly、Jean-Jacques Vasseur、Françoise Debart

  DOI：10.1002/ejoc.201901120

  日期：2019.10.17

  analogues mimicking the transition state of the 2'-O-methylation of the RNA in order to block viral 2'-O-methyltransferases and struggle against emerging viruses. Here we designed and synthesized five dinucleosides by connecting a 5'-thioadenosine representing the SAM to the 2'-OH of another adenosine unit mimicking the RNA substrate, via various sized sulfur-containing linkers such as alkylthioether

  病毒 RNA 2'-O-甲基转移酶在病毒感染期间通过催化核苷 N1 2'-OH 处 5'-末端 RNA 帽结构的甲基化或诱导使用 S-腺苷-L-甲硫氨酸 (SAM) 作为甲基供体，RNA 序列内腺苷的内部 2'-O-甲基化。我们的目标是合成模拟 RNA 2'-O-甲基化过渡状态的双底物 SAM 类似物，以阻断病毒 2'-O-甲基转移酶并对抗新兴病毒。在这里，我们通过将代表 SAM 的 5'-硫代腺苷连接到模拟 RNA 底物的另一个腺苷单元的 2'-OH，通过各种尺寸的含硫接头（例如烷基硫醚接头）设计并合成了五种双核苷，
• Selective inhibition of nicotinamide adenine dinucleotide kinases by dinucleoside disulfide mimics of nicotinamide adenine dinucleotide analogues
  作者：Riccardo Petrelli、Yuk Yin Sham、Liqiang Chen、Krzysztof Felczak、Eric Bennett、Daniel Wilson、Courtney Aldrich、Jose S. Yu、Loredana Cappellacci、Palmarisa Franchetti、Mario Grifantini、Francesca Mazzola、Michele Di Stefano、Giulio Magni、Krzysztof W. Pankiewicz

  DOI：10.1016/j.bmc.2009.06.013

  日期：2009.8

  Diadenosine disulfide (5) was reported to inhibit NAD kinase from Lysteria monocytogenes and the crystal structure of the enzyme-inhibitor complex has been solved. We have synthesized tiazofurin adenosine disulfide (4) and the disulfide 5, and found that these compounds were moderate inhibitors of human NAD kinase (IC50 = 110 mu M and IC50 = 87 mu M, respectively) and Mycobacterium tuberculosis NAD kinase (IC50 = 80 mu M and IC50 = 45 mu M, respectively). We also found that NAD mimics with a short disulfide (-S-S-) moiety were able to bind in the folded (compact) conformation but not in the common extended conformation, which requires the presence of a longer pyrophosphate (-O-P-O-P-O-) linkage. Since majority of NAD-dependent enzymes bind NAD in the extended conformation, selective inhibition of NAD kinases by disulfide analogues has been observed. Introduction of bromine at the C8 of the adenine ring restricted the adenosine moiety of diadenosine disulfides to the syn conformation making it even more compact. The 8-bromoadenosine adenosine disulfide (14) and its di(8-bromoadenosine) analogue (15) were found to be the most potent inhibitors of human (IC50 = 6 mu M) and mycobacterium NAD kinase (IC50 = 14-19 mu M reported so far. None of the disulfide analogues showed inhibition of lactate-, and inosine monophosphate-dehydrogenase (IMPDH), enzymes that bind NAD in the extended conformation. (C) 2009 Elsevier Ltd. All rights reserved.
• METHOD FOR IDENTIFYING INHIBITORS USING A HOMOLOGY MODEL OF POLO-LIKE KINASE 1
  申请人：Cyclacel Limited

  公开号：EP1683056A2

  公开（公告）日：2006-07-26
• [EN] METHOD<br/>[FR] PROCEDE
  申请人：CYCLACEL LTD

  公开号：WO2005047526A2

  公开（公告）日：2005-05-26

  The present invention relates to a homology model for PLK, and the use thereof in assays for the indentification of small molecule PLK modulators. The invention further relates to PLK modulators identified by said assays, and their use in the treatment of PLK-related disorders such as proliferative disorders.