Trifluoro-methanesulfonic acid (2R,3S,4R,5R)-2-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-4-(tetrahydro-pyran-2-yloxy)-5-(tetrahydro-pyran-2-yloxymethyl)-tetrahydro-furan-3-yl ester | 200404-37-1

• 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: Trifluoro-methanesulfonic acid (2R,3S,4R,5R)-2-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-4-(tetrahydro-pyran-2-yloxy)-5-(tetrahydro-pyran-2-yloxymethyl)-tetrahydro-furan-3-yl ester
• 英文别名: n2-Isobutyryl-9-(3',5'-di-o-[tetrahydropyran-2-yl]-2'-o-trifluoromethylsulfonyl-beta-d-arabinofuranosyl)guanine；[(2R,3S,4R,5R)-2-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]-4-(oxan-2-yloxy)-5-(oxan-2-yloxymethyl)oxolan-3-yl] trifluoromethanesulfonate
• CAS: 200404-37-1
• 化学式: C₂₅H₃₄F₃N₅O₁₀S
• 分子量: 653.634
• InChiKey: CBDYGHRSIBXTMD-SOPVAWBASA-N

物化性质

• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  186
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  Trifluoro-methanesulfonic acid (2R,3S,4R,5R)-2-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-4-(tetrahydro-pyran-2-yloxy)-5-(tetrahydro-pyran-2-yloxymethyl)-tetrahydro-furan-3-yl ester 在 吡啶 、 tert-butyl-ammonium fluoride 、 Dowex 50W x 2-100 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 10.0h， 生成 5'-O-(4,4'-二甲氧基三苯甲基)-N2-异丁酰基-2'-氟脱氧鸟苷
  参考文献：
  名称：

  Uniformly modified 2'-deoxy-2'-fluoro-phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets

  摘要：

  均一化修饰的磷酸二酯或硫代磷酸酯寡核苷酸，包含2'-脱氧-2'-氟腺苷、-鸟苷、-尿苷和-胞苷，首次在此报道，当它们与RNA杂交时，表现出一致的叠加性稳定性提升，同时不会影响碱基配对的特异性。2'-脱氧-2'-氟修饰的寡核苷酸与RNA杂交的圆二色光谱表明，杂交双链呈现完全的A型构象。以磷酸二酯形式存在的2'-脱氧-2'-氟修饰的寡核苷酸对核酸酶不具抵抗力；然而，以硫代磷酸酯形式存在的修饰寡核苷酸则具有极高的核酸酶抗性，并且保留了对RNA靶标的卓越结合亲和力。2'-脱氧-2'-氟修饰对RNA-DNA双链的稳定化效果被证明优于2'-O-甲基核糖的替代。与均一化2'-脱氧-2'-氟修饰寡核苷酸形成的RNA杂交双链不支持HeLa细胞中RNase H活性；然而，将修饰引入到“嵌合”寡核苷酸中已被证明可以激活哺乳动物的RNase H。均一化修饰的2'-脱氧-2'-氟硫代磷酸酯寡核苷酸提供了反义分子，具有（1）对RNA靶标的高结合亲和力和选择性，以及（2）对核酸酶的稳定性。

  DOI：

  10.1021/jm00059a007
• 作为产物：
  描述：

  9-Β-D-糖呋喃鸟嘌呤 在 吡啶 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 三甲基氯硅烷 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 Trifluoro-methanesulfonic acid (2R,3S,4R,5R)-2-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-4-(tetrahydro-pyran-2-yloxy)-5-(tetrahydro-pyran-2-yloxymethyl)-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  An Efficient and Scalable Synthesis of Arabinosylguanine and 2′-Deoxy-2′-Fluoro-guanosine

  摘要：

  An efficient conversion from commercially available 2,6-diaminopurine-2',3',5'-tri-O-benzyl arabinoside to arabinosylguanine and its further transformation to 2'-deoxy-2'-fluoro-guanosine is outlined. This process has been used to produce more than one hundred grams of final product.

  DOI：

  10.1080/07328319708006246

文献信息

• Sugar modified oligonucleotides
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20030004325A1

  公开（公告）日：2003-01-02

  Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

  提供了治疗和诊断易受到选定蛋白质产生调节的疾病的组合物和方法。根据优选实施例，提供了可以与RNA或DNA的选定序列特异性杂交的寡核苷酸和寡核苷酸类似物，其中核苷酸单元中至少有一个2'-脱氧呋喃糖苷基团被修饰。提供了治疗由各种病毒和其他致病因子引起的疾病的方法。
• Oligoribonucleotides and ribonucleases for cleaving RNA
  申请人：——

  公开号：US20030096287A1

  公开（公告）日：2003-05-22

  Oligomeric compounds including oligoribonucleotides and oligoribonucleosides are provided that have subsequences of 2′-pentoribofuranosyl nucleosides that activate dsRNase. The oligoribonucleotides and oligoribonucleosides can include substituent groups for increasing binding affinity to complementary nucleic acid strand as well as substituent groups for increasing nuclease resistance. The oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics. Also included in the invention are mammalian ribonucleases, i.e., enzymes that degrade RNA, and substrates for such ribonucleases. Such a ribonuclease is referred to herein as a dsRNase, wherein “ds” indicates the RNase's specificity for certain double-stranded RNA substrates. The artificial substrates for the dsRNases described herein are useful in preparing affinity matrices for purifying mammalian ribonuclease as well as non-degradative RNA-binding proteins.

  提供了包括寡核苷酸和寡核苷的寡聚化合物，其中包含2'-戊糖核苷酸亚序列，可以激活dsRNase。这些寡核苷酸和寡核苷可以包括取代基团，以增加与互补核酸链的结合亲和力，以及取代基团，以增加核酸酶抵抗力。这些寡聚化合物可用于诊断和其他研究目的，用于调节生物体内蛋白质的表达，以及用于诊断、检测和治疗其他易感于寡核苷酸治疗的疾病。本发明还包括哺乳动物核酸酶，即降解RNA的酶，以及这些核酸酶的底物。这样的核酸酶在本文中被称为dsRNase，其中“ds”表示RNase对某些双链RNA底物的特异性。本文所描述的dsRNases的人工底物可用于制备亲和力基质，以纯化哺乳动物核酸酶以及非降解的RNA结合蛋白。
• 2'-MODIFIED OLIGONUCLEOTIDES
  申请人：Cook Dan Phillip

  公开号：US20080032945A1

  公开（公告）日：2008-02-07

  Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

  本发明提供了用于治疗和诊断对调节所选蛋白质产生敏感的疾病的组合物和方法。根据优选实施例，提供了可以与RNA或DNA的所选序列特异性杂交的寡核苷酸和寡核苷酸类似物，其中核苷酸单元的至少一个2'-脱氧呋喃糖基团被修改。提供了治疗由各种病毒和其他致病因子引起的疾病的方法。
• 2'-Modified Oligonucleotides
  申请人：Cook Phillip Dan

  公开号：US20090198047A1

  公开（公告）日：2009-08-06

  Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

  本发明提供了用于治疗和诊断适于调节所选蛋白质产生的疾病的组合物和方法。根据优选实施例，提供了可以与RNA或DNA的选定序列特异性杂交的寡核苷酸和寡核苷酸类似物，其中核苷酸单元的至少一个2'-脱氧呋喃糖苷基团被修饰。提供了治疗由各种病毒和其他致病因子引起的疾病的方法。
• Sugar modified oligonucleotides that detect and modulate gene expression
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：EP1443051A2

  公开（公告）日：2004-08-04

  Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2'-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of HIV, herpes virus, papillomavirus and other infections is provided.

  本发明提供了用于治疗和诊断可调节特定蛋白质产生的疾病的组合物和方法。根据优选的实施方案，提供了寡核苷酸和寡核苷酸类似物，它们可与选定的 RNA 或 DNA 序列特异性杂交，其中核苷单元的 2'-deoxyfuranosyl 分子中至少有一个被修饰。提供了艾滋病毒、疱疹病毒、乳头状瘤病毒和其他感染的治疗方法。