6-methoxypurine riboside | 5746-29-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 6-methoxypurine riboside
• 英文别名: 6-methoxy-9-(β-D-ribofuranosyl)purine；6-Methoxy-purin-ribosid；6-O-methyl inosine；NSC 30306；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-methoxypurin-9-yl)oxolane-3,4-diol
• CAS: 5746-29-2
• 化学式: C₁₁H₁₄N₄O₅
• 分子量: 282.256
• InChiKey: UQQHOWKTDKKTHO-IOSLPCCCSA-N

物化性质

• 熔点：
  140 °C(Solv: methanol (67-56-1); ethyl acetate (141-78-6))
• 沸点：
  610.7±65.0 °C(Predicted)
• 密度：
  1.84±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P501,P270,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313,P301+P312+P330
• 危险性描述：
  H302,H315,H319

制备方法与用途

O-甲基肌苷是一种类似次黄嘌呤的化合物，次黄嘌呤主要存在于肌肉组织中，是黄嘌呤在嘌呤氧化酶作用下产生的代谢产物。它具有典型的抗炎作用，并且可能作为一种潜在的内源性聚ADP核糖聚合酶(PARP)抑制剂发挥作用。次黄嘌呤能够通过抑制PARP活性、减少过氧亚硝酸盐诱导的线粒体去极化及次生超氧化物的生成，从而起到细胞保护作用。此外，次黄嘌呤也可用作缺氧状态的指示剂[1][2]。

反应信息

• 作为反应物：
  描述：

  6-methoxypurine riboside 在 2,2'-二硫二吡啶 、 磷酸三乙酯 、 三苯基膦 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists

  摘要：

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.

  DOI：

  10.1021/jm401497a
• 作为产物：
  描述：

  2',3',5'-三乙酰腺苷 在 吡啶 、 Dowex 1*2 (OH^-) resin 、 水 作用下， 反应 20.0h， 生成 6-methoxypurine riboside
  参考文献：
  名称：

  Efficient Conversion of 6-Aminopurines and Nucleosides into 6-Substituted Analogs via Novel 6-(1,2,4-Triazol-4-yl)purine Derivatives.

  摘要：

  DOI：

  10.1021/ja00099a061

文献信息

• Anti-HCV nucleoside derivatives
  申请人：——

  公开号：US20030008841A1

  公开（公告）日：2003-01-09

  The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

  本发明涉及新颖和已知的嘌呤和嘧啶核苷衍生物，已发现这些衍生物对丙型肝炎病毒（HCV）具有活性。本发明声明利用这些衍生物治疗HCV感染，以及本文所披露的新颖核苷衍生物。
• Selective Functionalization of Aminoheterocycles by a Pyrylium Salt
  作者：Daniel Moser、Yaya Duan、Feng Wang、Yuanhong Ma、Matthew J. O'Neill、Josep Cornella

  DOI：10.1002/anie.201806271

  日期：2018.8.20

  The functionalization of aminoheterocycles by using a pyrylium tetrafluoroborate reagent (Pyry‐BF4) is presented. This reagent efficiently condenses with a great variety of heterocyclic amines and primes the C−N bond for nucleophilic aromatic substitution. More than 60 examples for the formation of C−O, C−N, C−S, or C−SO2R bonds are disclosed herein. In contrast to C−N activation through diazotization

  提出了使用四氟硼酸吡啶鎓试剂（Pyry-BF 4）对氨基杂环进行官能化的方法。该试剂可与多种杂环胺有效地缩合，并为亲核芳香族取代反应准备C-N键。本文公开了用于形成CO，CN，CS或CS 2 R键的60多个例子。与通过重氮化和多烷基化进行CN活化相反，该方法的特点是条件温和且对官能团的耐受力强。除小分子衍生化外，Pyry-BF 4还允许以后期方式引入官能团，以提供高度官能化的结构。
• Production, Characterization and Synthetic Application of a Purine Nucleoside Phosphorylase from<i>Aeromonas hydrophila</i>
  作者：Daniela Ubiali、Carla D. Serra、Immacolata Serra、Carlo F. Morelli、Marco Terreni、Alessandra M. Albertini、Paolo Manitto、Giovanna Speranza

  DOI：10.1002/adsc.201100505

  日期：2012.1

  6‐aminopurine (deoxy)ribonucleosides. A library of nucleoside analogues was synthesized and then submitted to enzymatic phosphorolysis as well. This assay revealed that 1‐, 2‐, 6‐ and 7‐modified nucleosides are accepted as substrates, whereas 8‐substituted nucleosides are not. A few transglycosylation reactions were carried out using 7‐methylguanosine iodide (4) as a D‐ribose donor and 6‐substituted purines

  由deoD基因编码的嗜水气单胞菌的嘌呤核苷磷酸化酶（PNP）已在大肠杆菌中过表达，纯化，表征了其底物特异性，并用于一些6取代的嘌呤9-核糖苷的制备性合成。对天然核苷的底物特异性表明，该PNP催化6-氧代嘌呤和6-氨基嘌呤（脱氧）核糖核苷的磷酸水解。合成了核苷类似物的文库，然后也进行了酶促磷酸解。该测定法揭示了1、2、6和7修饰的核苷被接受为底物，而8取代的核苷则不被接受。使用7-甲基鸟苷碘化物进行了一些转糖基化反应（4）作为D核糖供体，6取代的嘌呤作为受体。特别是，按照这种方法，可以使用2-氨基-6氯嘌呤9核苷（2c），6-甲氧基嘌呤9核苷（2d）和2-氨基6（甲硫基）嘌呤9核苷（2g）合成的收率和纯度都很高。
• Method for producing nucleoside-5'-phosphate ester
  申请人：——

  公开号：US20020004590A1

  公开（公告）日：2002-01-10

  A method for producing nucleoside-5′-phosphate esters inexpensively and in high yields by phosphorylating a nucleoside with a phospahte group donor using an acid phosphatase having an increased affinity for the nucleoside and/or an increased temperature stability at a pH of pH 3.0 to 5.5, to produce a nucleoside-5′-phosphate ester. Mutant acid phosphatases having increased affinty for nucleosides and/or an enhanced temperature stability are also provided.

  一种制备核苷酸5'-磷酸酯的方法，通过使用具有对核苷酸增加亲和力和/或在pH 3.0至5.5的条件下具有增强温度稳定性的酸性磷酸酶，用磷酸供体对核苷酸进行磷酸化，以低成本高产率地制备核苷酸5'-磷酸酯。还提供了具有增强核苷酸亲和力和/或增强温度稳定性的突变酸性磷酸酶。
• Improved Synthesis of Phosphoramidite-Protected N6-Methyladenosine via BOP-Mediated SNAr Reaction
  作者：Shifali Shishodia、Christopher J. Schofield

  DOI：10.3390/molecules26010147

  日期：——

  N6-methyladenosine(m6A) is the most abundant modification in mRNA. Studies on proteins that introduce and bind m6A require the efficient synthesis of oligonucleotides containing m6A. We report an improved five-step synthesis of the m6A phosphoramidite starting from inosine, utilising a 1-H-benzotriazol-1-yloxytris(dimethylamino)phosphoniumhexafluorophosphate (BOP)-mediated SNAr reaction in the key

  N6-甲基腺苷 (m6A) 是 mRNA 中最丰富的修饰。对引入和结合 m6A 的蛋白质的研究需要有效合成含有 m6A 的寡核苷酸。我们报告了从肌苷开始的 m6A 亚磷酰胺的改进的五步合成，在关键步骤中利用 1-H-苯并三唑-1-基氧基三（二甲氨基）鏻六氟磷酸盐（BOP）介导的 SNAr 反应。与报道的路线相比，该路线的总产量显着增加，并且可用于合成其他腺苷衍生物的亚磷酰胺，例如乙醇腺苷，一种由重要的抗癌药物卡莫司汀形成的 DNA 加合物的 RNA 类似物。