6-硫代肌苷 5'-单磷酸酯 | 53-83-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 中文名称: 6-硫代肌苷 5'-单磷酸酯
• 中文别名: 6-硫代肌苷5'-单磷酸酯
• 英文名称: {[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-sulfanyl-9H-purin-9-yl)oxolan-2-yl]methoxy}phosphonic acid
• 英文别名: 9-(β-D-ribofuranosyl)-6-mercaptopurine 5'-monophosphate；6-mercaptopurineriboside 5'-monophosphate；6-thioinosine 5' monophosphate；6-thioinosine-5'-monophosphate；6-thioinosine phosphate；6-thioinosine monophosphate；Thioinosinic acid；[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-sulfanylidene-3H-purin-9-yl)oxolan-2-yl]methyl dihydrogen phosphate
• CAS: 53-83-8
• 化学式: C₁₀H₁₃N₄O₇PS
• 分子量: 364.276
• InChiKey: ZKRFOXLVOKTUTA-KQYNXXCUSA-N

物化性质

• 熔点：
  149-155°C (dec.)
• 沸点：
  833.4±75.0 °C(Predicted)
• 密度：
  2.25±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热）、水（轻微、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  23
• 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：
  191
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-硫代肌苷 5'-单磷酸酯 在 2,2'-二硫二吡啶 、 Aplysia californica ADP-ribosyl cyclase 、 碳酸氢钠 、 magnesium sulfate 、 三苯基膦 、 manganese(ll) chloride 作用下， 以 formamide 、 二甲基亚砜 为溶剂， 反应 31.0h， 生成 cyclic 6-thioinosine 5'-diphosphate ribose
  参考文献：
  名称：

  Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

  摘要：

  Two nicotinamide adenine dinucleotide (NAD(+)) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD(+) (6-N-methyl nicotinamide adenosine 5'-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5'-diphosphoribose, 11), whereas 6-thio NHD+ (nicotinamide 6-mercaptopurine 5'-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5'-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5'-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5'-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling.

  DOI：

  10.1021/jm201127y
• 作为产物：
  描述：

  6-氯嘌呤核糖甙-5'-O-单磷酸酯钠盐 在 水 、 potassium hydrosulfide 作用下， 生成 6-硫代肌苷 5'-单磷酸酯
  参考文献：
  名称：

  Nucleotides. I. Syntheses of 6-Chloro-, 6-Mercapto-, and 2-Amino-6-mercapto-9-β-D-ribofuranosylpurine 5'-Phosphates¹

  摘要：

  DOI：

  10.1021/ja01462a030

文献信息

• [EN] TANKYRASE INHIBITORS<br/>[FR] INHIBITEURS DE TANKYRASE
  申请人：UNIV BATH

  公开号：WO2014087165A1

  公开（公告）日：2014-06-12

  The present invention relates to a compound of formula I wherein X is C(R6) or N, Y is C or N, and ring A, ring B, R1 and R2 have the meanings defined herein, provided that when ring B is carbocyclic, X is C(R6); or a pharmaceutically acceptable salt or solvate thereof. The compounds are tankyrase-1 and tankyrase-2 inhibitors and are useful in the treatment of a number of conditions, including cancer.

  本发明涉及一种具有式I的化合物，其中X为C(R6)或N，Y为C或N，环A、环B、R1和R2具有本文中定义的含义，前提是当环B为碳环时，X为C(R6)；或其药学上可接受的盐或溶剂。这些化合物是坦克酶-1和坦克酶-2抑制剂，并可用于治疗多种疾病，包括癌症。
• Thermophilic phosphoribosyltransferases <i>Thermus thermophilus</i> HB27 in nucleotide synthesis
  作者：Ilja V Fateev、Ekaterina V Sinitsina、Aiguzel U Bikanasova、Maria A Kostromina、Elena S Tuzova、Larisa V Esipova、Tatiana I Muravyova、Alexei L Kayushin、Irina D Konstantinova、Roman S Esipov

  DOI：10.3762/bjoc.14.289

  日期：——

  Phosphoribosyltransferases are the tools that allow the synthesis of nucleotide analogues using multi-enzymatic cascades. The recombinant adenine phosphoribosyltransferase (TthAPRT) and hypoxanthine phosphoribosyltransferase (TthHPRT) from Thermus thermophilus HB27 were expressed in E.coli strains and purified by chromatographic methods with yields of 10-13 mg per liter of culture. The activity dependence

  磷酸核糖基转移酶是允许使用多酶级联反应合成核苷酸类似物的工具。来自嗜热栖热菌HB27的重组腺嘌呤磷酸核糖基转移酶（TthAPRT）和次黄嘌呤磷酸核糖基转移酶（TthHPRT）在大肠杆菌菌株中表达并通过色谱法纯化，每升培养物产量为10-13mg。研究了TthAPRT和TthHPRT对不同因素的活性依赖性，以及对不同杂环碱基的底物特异性。确定了具有天然底物的TthHPRT的动力学参数。使用TthAPRT和1-（β-D-呋喃呋喃糖基）吡唑并[3,4-d]嘧啶合成了两个核苷酸：9-（β-D-呋喃呋喃糖基）-2-氯腺嘌呤5'-单磷酸酯（2-Сl-AMP）使用TthНPRT的-4-one 5'-单磷酸盐（Allop-MP）。
• Five-Component Cascade Synthesis of Nucleotide Analogues in an Engineered Self-Immobilized Enzyme Aggregate
  作者：Robert A. Scism、Brian O. Bachmann

  DOI：10.1002/cbic.200900620

  日期：——

  Pathway in a particle: A five‐enzyme biosynthetic pathway was self‐immobilized to form a single biocatalyst for generation of purine nucleotide analogues from D‐ribose. This method provides an alternative to engineering biosynthetic pathways in whole cells that obviates problems associated with toxicity, transport and genetic regulation.

  颗粒中的途径：五种酶的生物合成途径是自固定的，可形成单一的生物催化剂，用于从D-核糖生成嘌呤核苷酸类似物。该方法提供了一种工程化全细胞生物合成途径的替代方法，从而消除了与毒性，转运和基因调控有关的问题。
• SYNTHESIS OF ARA-2'-O-METHYL-NUCLEOSIDES, CORRESPONDING PHOSPHORAMIDITES AND OLIGONUCLEOTIDES INCORPORATING NOVEL MODIFICATIONS FOR BIOLOGICAL APPLICATION IN THERAPEUCTICS, DIAGNOSTICS, G- TETRAD FORMING OLIGONUCLEOTIDES AND APTAMERS
  申请人：Srivastava Suresh C.

  公开号：US20120149888A1

  公开（公告）日：2012-06-14

  The present invention relates to synthesis, purification and methods to obtain high purity novel 2′-arabino-O-methyl nucleosides and the corresponding phosphoramidites of various arabinonucleoside bases and introduction of such units into defined sequence synthetic DNA and RNA. Various synthetic oligonucleotides, such as HIV integrase inhibitor 14-mer and thrombin binding oligonucleotide, thrombin-1, bearing ara-2′-omethyl modification have been synthesized. It is anticipated the oligonucleotides incorporating these monomers will exhibit biological activities related to antisense approach approach, design of better SiRNA's, diagnostic agents. Similarly, it is anticipated that oligonucleotides incorporating such novel nucleosides will be useful to develop therapeutic candidates designing stable G-quadruplexes and Aptamers for oligonucleotide structure, folding topology, evaluation of biochemical properties and design and develop as therapeutic agents. It is further anticipated that the nucleosides, phosphates and triphosphates of this invention could develop as therapeutic agents.

  本发明涉及合成、纯化和获取高纯度新型2'-阿拉伯核苷-O-甲基核苷和各种阿拉伯核苷基的相应磷酰胺酯的方法，并将这些单元引入到定义的序列合成DNA和RNA中。已合成了各种合成寡核苷酸，例如HIV整合酶抑制剂14-mer和凝血酶结合寡核苷酸，凝血酶-1，带有ara-2'-omethyl修饰。预计包含这些单体的寡核苷酸将展示与反义方法、更好的SiRNA设计、诊断剂相关的生物学活性。同样，预计包含这些新型核苷的寡核苷酸将有助于开发稳定的G四链体和寡核苷酸结构的Aptamers，用于寡核苷酸结构、折叠拓扑、生化特性的评估和设计和开发为治疗剂。进一步预计，本发明的核苷、磷酸盐和三磷酸盐可作为治疗剂开发。
• Use of pimecrolimus for selective immunomodulation
  申请人：Novartis AG

  公开号：EP1649856A2

  公开（公告）日：2006-04-26

  The invention relates to methods to produce selective immunomodulation in epithelial tissues to treat epithelial inflammatory disorders. This invention provides methods for the use of pimecrolimus to treat epithelial inflammatory disorders including asthma and inflammatory bowel disease while minimizing systemic side effects.

  本发明涉及在上皮组织中产生选择性免疫调节以治疗上皮炎症性疾病的方法。本发明提供了使用吡美莫司治疗上皮炎症性疾病（包括哮喘和炎症性肠病）的方法，同时将全身副作用降至最低。