N-(9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrothiophen-2-yl)-9H-purin-6-yl)benzamide | 159981-08-5

• 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: N-(9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrothiophen-2-yl)-9H-purin-6-yl)benzamide
• 英文别名: N-Benzoyl-4'-thioadenosine；N-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)thiolan-2-yl]purin-6-yl]benzamide
• CAS: 159981-08-5
• 化学式: C₁₇H₁₇N₅O₄S
• 分子量: 387.419
• InChiKey: NZMQTSLCENJVBH-CNEMSGBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrothiophen-2-yl)-9H-purin-6-yl)benzamide 在 吡啶 、 咪唑 、 叔丁基二甲基氯硅烷 作用下， 反应 22.0h， 生成 N-(9-((2R,3R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-((tert-butyldimethylsilyl)oxy)-4-hydroxytetrahydrothiophen-2-yl)-9H-purine-6-yl)benzamide
  参考文献：
  名称：

  环状二核苷酸化合物、其制备方法和应用

  摘要：

  本发明公开了环状二核苷酸化合物、其制备方法和应用，具体涉及一种式(I)所示的化合物，其药学上可接受的盐，其制备方法以及其在制备用于治疗和/或预防与激活STING蛋白相关的疾病的药物中的应用或作为疫苗佐剂的应用。所述与激活STING蛋白相关的疾病包括病毒感染，细菌感染，癌症，免疫系统相关疾病等。

  公开号：

  CN109694397B
• 作为产物：
  描述：

  ((3aS,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)methanol 在 吡啶 、 三甲基氯硅烷 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.5h， 生成 N-(9-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrothiophen-2-yl)-9H-purin-6-yl)benzamide
  参考文献：
  名称：

  [EN] CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS
  [FR] COMPOSÉS DINUCLÉOTIDIQUES CYCLIQUES UTILISÉS COMME AGONISTES STING

  摘要：

  一类具有通用公式（I）的多环化合物的类别，其中Base1，Base2，Y，Za，Xa，Xa1，Xb，Xb1，Xc，Xc1，Xd，Xd1，R1，R1a，R2，R2a，R3，R4，R4a，R5，R6，R6a，R7，R7a，R8，R8a和R9按本说明书中定义，可能对作为I型干扰素产生的诱导剂特别有用，具体作为STING激活剂。还提供了合成和使用化合物的过程。

  公开号：

  WO2019125974A1

文献信息

• 4'-Thio-β-D-oligoribonucleotides: Nuclease Resistance and Hydrogen Bonding Properties
  作者：C. Leydier、L. Bellon、J. -L. Barascut、J. -L. Imbach

  DOI：10.1080/15257779508012526

  日期：1995.5.1

  The syntheses and the study of nuclease resistance and hydrogen bonding of modified oligoribonucleotides, i.e. 4'-thio-beta-D-oligoribonucleotides (4'-S-RNA), are reported.
• 4′-Thio-RNA: Synthesis, Base Pairing Properties and Interaction with Dimerization Initiation Site of HIV-1
  作者：David Dukhan、Florence De Valette、Roland Marquet、Bernard Ehresmann、Chantal Ehresmann、François Morvan、Jean-Louis Barascut、Jean-Louis Imbach

  DOI：10.1080/07328319908044740

  日期：1999.6

  In the present paper, we describe the synthesis of a modified 9-mer oligonucleotide, 4'-S-r(UGUGCACCU) containing for the first time 4'-thio-guanosine units. This modified 9-mer was found to inhibit in vitro genomic RNA dimerization as well as the wild type RNA.
• Investigations toward the selection of fully-modified 4′-thioRNA aptamers: Optimization of in vitro transcription steps in the presence of 4′-thioNTPs
  作者：Noriaki Minakawa、Mioko Sanji、Yuka Kato、Akira Matsuda

  DOI：10.1016/j.bmc.2008.09.048

  日期：2008.11

  We describe herein a method for isolating fully-modified 4 '-thioRNA aptamers against human alpha-thrombin using the SELEX protocol. In order to isolate the desired aptamers, in vitro transcription was examined in the presence of four kinds of 4 '-thioribonucleoside triphosphates (4 '-thioNTPs) in an effort to afford the fully-modified 4 '-thioRNA. The transcription efficiency of the 4 '-thioNTPs was first compared with that of the nucleoside 5 '-(alpha-thio)triphosphates (alpha SNTPs) and found to be less effective than that of the aSNTPs, especially when GTP and/or ATP were substituted for 4 '-thioGTP and/or 4 '-thioATP. Further attempts to improve its efficiency, including the use of a mutant RNA polymerase instead of the wild type, various additives, and 4 '-thioNTP concentrations were unsuccessful. Accordingly, the transcription was performed in the presence of 4 '-thioNTPs together with the natural GTP and ATP at the appropriate concentrations. Although this attempt furnished a highly-modified 4 '-thioRNA, but not a fully-modified 4 '-thioRNA, we eventually succeeded in isolating the fully-modified 4 '-thioRNA aptamers by SELEX using optimized transcription conditions, followed by post-modification of the resulting aptamers. (C) 2008 Elsevier Ltd. All rights reserved.
• CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：EP3727401A1

  公开（公告）日：2020-10-28
• [EN] CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS<br/>[FR] COMPOSÉS DINUCLÉOTIDIQUES CYCLIQUES UTILISÉS COMME AGONISTES STING
  申请人：MERCK SHARP & DOHME

  公开号：WO2019125974A1

  公开（公告）日：2019-06-27

  A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Za, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

  一类具有通用公式（I）的多环化合物的类别，其中Base1，Base2，Y，Za，Xa，Xa1，Xb，Xb1，Xc，Xc1，Xd，Xd1，R1，R1a，R2，R2a，R3，R4，R4a，R5，R6，R6a，R7，R7a，R8，R8a和R9按本说明书中定义，可能对作为I型干扰素产生的诱导剂特别有用，具体作为STING激活剂。还提供了合成和使用化合物的过程。