2-chloro-2'-deoxyinosine | 136834-39-4

• 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: 2-chloro-2'-deoxyinosine
• 英文别名: 2-Chloro-2'-deoxyinosine；2-chloro-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one
• CAS: 136834-39-4
• 化学式: C₁₀H₁₁ClN₄O₄
• 分子量: 286.675
• InChiKey: PFZWCXFVGJYNGP-KVQBGUIXSA-N

物化性质

• 密度：
  2.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 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：
  109
• 氢给体数：
  3
• 氢受体数：
  6

制备方法与用途

2-氯-2'-脱氧肌苷是一种嘌呤核苷类似物，广泛用于对抗肿瘤，特别是针对惰性淋巴系统恶性肿瘤。其抗癌机制主要通过抑制DNA合成和诱导细胞凋亡来实现。

反应信息

• 作为反应物：
  描述：

  2-chloro-2'-deoxyinosine 在 吡啶 、 三乙胺 作用下， 以 乙二醇甲醚 为溶剂， 生成 Diphenyl-carbamic acid 9-((2R,3aS,9aR)-5,5,7,7-tetraisopropyl-tetrahydro-1,4,6,8-tetraoxa-5,7-disila-cyclopentacycloocten-2-yl)-2-[3-(2,2,2-trifluoro-acetylamino)-propylamino]-9H-purin-6-yl ester
  参考文献：
  名称：

  带有阳离子基团的寡核苷酸：N 2-（3-氨基丙基）脱氧鸟苷。合成，增强的结合性能和结合化学

  摘要：

  已经合成了具有位于2'-脱氧guonosine的N 2-位的氨丙基的亚磷酰胺，并将其掺入寡核苷酸中。这种修饰显示出增强的针对DNA和RNA靶的结合特性，可用于缀合其他功能。

  DOI：

  10.1016/0040-4039(96)01755-8
• 作为产物：
  描述：

  2,6-二氯-9-(3,5-二-O-对甲苯甲酰基-2-脱氧-beta-D-赤式-呋喃戊糖基)嘌呤 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 乙醇 为溶剂， 生成 2-chloro-2'-deoxyinosine
  参考文献：
  名称：

  Remarkable enhancement of binding affinity of Heterocycle-modified DNA to DNA and RNA. Synthesis, characterization and biophysical evaluation of N2-imidazolylpropylguanine and N2-imidazolylpropyl-2-aminoadenine modified oligonucleotides

  摘要：

  Oligonucleotides containing novel N-2-Imidazolylpropylguanine and N-2-Imidazolylpropyl-2-aminoadenine moieties were synthesized and studied for their hybridization and biophysical properties. Interestingly, these heterocycle modified oligonucleotides showed a remarkable enhancement of heteroduplex binding affinity when hybridized to complementary DNA.

  DOI：

  10.1016/s0040-4039(00)76514-2

文献信息

• 2-Substituted 2′-deoxyinosine 5′-triphosphates as substrates for polymerase synthesis of minor-groove-modified DNA and effects on restriction endonuclease cleavage
  作者：Ján Matyašovský、Michal Hocek

  DOI：10.1039/c9ob02502b

  日期：——

  Five 2-substituted 2'-deoxyinosine triphosphates (dRITP) were synthesized and tested as substrates in enzymatic synthesis of minor-groove base-modified DNA. Only 2-methyl and 2-vinyl derivatives proved to be good substrates for Therminator DNA polymerase, whilst all other dRITPs and other tested DNA polymerases did not give full length products in primer extension. The DNA containing 2-vinylhypoxanthine

  合成了五种2-取代的2'-脱氧肌苷三磷酸酯（dRITP），并作为酶法合成了小沟碱基修饰的DNA的底物。事实证明，只有2-甲基和2-乙烯基衍生物是Therminator DNA聚合酶的良好底物，而所有其他dRITP和其他经过测试的DNA聚合酶在引物延伸方面均未提供全长产物。然后通过与硫醇的硫醇-烯反应进一步修饰含有2-乙烯基次黄嘌呤的DNA。由于小槽内硫醇与乙烯基之间的邻近作用，含半胱氨酸的小槽结合十二肽与DNA之间发生了交联反应。2位取代的dIRTP，以及先前制备的2位取代的2' 然后，将三磷酸脱氧腺苷（dRATP）酶促合成小沟槽修饰的DNA，以研究小沟槽修饰对II型限制性核酸内切酶（REs）切割DNA的影响。尽管RE应该通过大槽中的H键识别序列，但是一些小槽修饰也对切割具有抑制作用。
• Antisense modulation of MDM2 expression
  申请人：——

  公开号：US20030203862A1

  公开（公告）日：2003-10-30

  Compounds, compositions and methods are provided for inhibiting the expression of human mdm2. The compositions include antisense compounds targeted to nucleic acids encoding mdm2. Methods of using these oligonucleotides for inhibition of mdm2 expression and for treatment of diseases such as cancers associated with overexpression of mdm2 are provided.

  提供了用于抑制人类mdm2表达的化合物、组合物和方法。这些组合物包括针对编码mdm2的核酸的反义物质。提供了使用这些寡核苷酸抑制mdm2表达和治疗与mdm2过度表达相关的癌症等疾病的方法。
• System for delivering therapeutic agents into living cells and cells nuclei
  申请人：Segev David

  公开号：US20060160763A1

  公开（公告）日：2006-07-20

  A novel class of oligomeric compounds designed for forming conjugates with biologically active substances and delivering these substances to a desired bodily target are disclosed. Novel conjugates of these oligomeric compounds and biologically active moieties, pharmaceutical compositions containing such conjugates, and uses thereof as delivery systems for delivering the biologically active substances to a desired target are further disclosed. Processes of preparing the conjugates and the oligomeric compounds and novel intermediates designed for and used in these processes are also disclosed.

  本发明披露了一种新型寡聚化合物，旨在与生物活性物质形成共轭物，并将这些物质传递到所需的身体靶点。本发明还披露了这些寡聚化合物和生物活性基团的新型共轭物，包含这种共轭物的药物组合物以及将其用作传递生物活性物质到所需靶点的传递系统的用途。本发明还披露了制备共轭物和寡聚化合物的过程以及设计和用于这些过程的新型中间体。
• Compound for detecting and modulating RNA activity and gene expression
  申请人：Isis Pharmaceuticals, Inc.

  公开号：US06262241B1

  公开（公告）日：2001-07-17

  Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferrably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferrably accomplished. Therapeutics, diagnostics and research methods and also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.

  本发明揭示了调节RNA和DNA活性的组合物和方法。根据优选实施例，制备了包含靶向部分和反应部分的反义组合物。反应部分可以通过磷酸二酯键断裂、骨架糖键断裂或碱基修饰等方式起作用。在本发明的某些实施例中，改善寡核苷酸的药效和药代动力学特性的基团也很有用。还可以通过将反应性或非反应性功能传递到与目标RNA杂交形成的小沟中来实现。本发明还揭示了治疗、诊断和研究方法。还提供了合成核苷酸和核苷酸片段，可用于制备寡核苷酸和寡核苷酸类似物。
• Compositions and methods for detecting and modulating rna activity and gene expression
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：EP1418179A2

  公开（公告）日：2004-05-12

  Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferably accomplished. Therapeutics, diagnostics and research methods are also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.

  本文公开了调节 RNA 和 DNA 活性的组合物和方法。根据优选的实施方案，反义组合物由靶向部分和反应部分组成。反应部分最好通过磷酸二酯键裂解、骨架糖键裂解或碱基修饰起作用。根据本发明的某些实施方案，改善寡核苷酸药效学和药代动力学特性的基团也是有用的。最好还能将反应性或非反应性官能团输送到组合物与目标 RNA 杂交形成的次凹槽中。本发明还公开了治疗、诊断和研究方法。本发明还提供了合成核苷和核苷片段，可用于制备用于上述目的的寡核苷酸和寡核苷酸类似物。