胸腺嘧啶脱氧核苷-5-羧酸 | 3544-99-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 胸腺嘧啶脱氧核苷-5-羧酸
• 中文别名: 胸苷-5'-羧酸
• 英文名称: thymidine-5'-carboxylic acid
• 英文别名: 1-β-(thymin-1-yl)-D-riburonic acid；(2S,3S,5R)-3-hydroxy-5-[5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]tetrahydrofuran-2-carboxylic acid；1-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-β-D-erythro-1,2-dideoxy-pentofuranuronic acid；(2S,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolane-2-carboxylic acid
• CAS: 3544-99-8
• 化学式: C₁₀H₁₂N₂O₆
• 分子量: 256.215
• InChiKey: TURHENGAFSXIAQ-XVMARJQXSA-N

物化性质

• 密度：
  1.596±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  胸腺嘧啶脱氧核苷-5-羧酸 在 borane-d3 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以71%的产率得到2'-脱氧(5'-14C)-3,4-二氢胸苷
  参考文献：
  名称：

  Isotope effects on the sequence-specific cleavage of DNA by neocarzinostatin: kinetic partitioning between 4'- and 5'-hydrogen abstraction at unique thymidine sites

  摘要：

  In this article it is shown that in certain sequences cleavage of DNA at thymidine residues by activated neocarzinostatin occurs via a rate-limiting abstraction of either a 4'- or 5'-hydrogen from the deoxyribose moiety and that this partitioning can be modulated by deuteriation at either position. An analysis by gel electrophoresis of the HindIII-BamHI restriction fragment (346 bp) of pBR322 revealed that in the first 45 nucleotides of the (+)-strand T14, T17, T27, and T44 are strongly sensitive to deuterium substitution at C-4' (k(H)/k(D) approximately 2.4-5.5) and are less sensitive to deuteriation at C-5' (k(H)/k(D) approximately 1.0-2.6). All four of these T sites are located in GT steps. Other T residues are cleaved and exhibit variable sensitivity to 5'-deuteriation; however, they show no evidence of 4'-chemistry. The 5'-radical intermediate yields 3'-phosphate termini. The 4'-radical intermediate is demonstrated to partition between a modified abasic carbohydrate terminus and a 3'-phosphoglycolate terminus. The relative ratio of these two termini is, in turn, modulated by the structure of the thiol activator/reductant.

  DOI：

  10.1021/ja00006a054
• 作为产物：
  描述：

  beta-胸苷 在 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 四丁基溴化铵 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 胸腺嘧啶脱氧核苷-5-羧酸
  参考文献：
  名称：

  几种白藜芦醇糖苷衍生物与次氯酸盐在各种介质中的反应

  摘要：

  紫檀芪苷（反式-3,5-二甲氧基芪-4'-O-β-D-葡萄糖苷）与白藜芦醇苷的Ar-O-Tr衍生物（3,5-二羟基芪-4'-O-β-D-葡萄糖苷）的反应) 和松芪苷（3-甲氧基-5-羟基芪-4'-O-β-D-葡萄糖苷）与 NaOCl 和 t-BuOCl 在稳定的硝酰基自由基 TEMPO 存在下在各种介质中进行了研究。发现紫檀芪苷转化的主要产物是其2,6-二氯衍生物，其中一部分被氧化形成2,6-二氯紫檀芪葡糖苷酸。白藜芦醇苷和松芪苷的三苯甲基醚与次氯酸盐反应形成产物混合物。

  DOI：

  10.1007/s10600-012-0146-z

文献信息

• Diketo acids with nucleobase scaffolds: anti-HIV replication inhibitors targeted at HIV integrase
  申请人：Nair Vasu

  公开号：US20060172973A1

  公开（公告）日：2006-08-03

  A new class of diketo acids constructed on nucleobase scaffolds, designed as inhibitors of HIV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described.

  一种新型的二酮酸类化合物，构建在核碱基支架上，设计为通过抑制HIV整合酶来抑制HIV复制，这些化合物可用于预防或治疗HIV感染，治疗艾滋病和ARC，可以作为化合物或药用盐的形式，与药用载体一起使用，单独或与抗病毒药物、免疫调节剂、抗生素、疫苗和其他治疗药物联合使用。还描述了治疗艾滋病和ARC的方法，以及治疗或预防HIV感染的方法。
• Diketo acids on nucleobase scaffolds as inhibitors of Flaviviridae
  申请人：Nair Vasu

  公开号：US20060223834A1

  公开（公告）日：2006-10-05

  A new class of diketo acids constructed on nucleobase scaffolds, designed as inhibitors of HCV replication through inhibition of HCV NS5B RNA polymerase, is described. These compounds are useful in the prevention or treatment of infection by HCV and in the treatment of other Flaviviridae infections, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents. Methods of treating HCV and methods of treating or preventing infection by HCV are also described.

  一种新型的二酮酸类化合物，构建在核碱基支架上，设计为通过抑制HCV NS5B RNA聚合酶来抑制HCV复制，这些化合物可用于预防或治疗HCV感染，以及治疗其他黄病毒科感染，可以作为化合物或药用盐的形式，与药用载体一起使用，单独或与抗病毒药物、免疫调节剂、抗生素、疫苗和其他治疗药物联合使用。还描述了治疗HCV的方法以及治疗或预防HCV感染的方法。
• Symmetrical and unsymmetrical <i>α</i>,<i>ω</i>-nucleobase amide-conjugated systems
  作者：Sławomir Boncel、Maciej Mączka、Krzysztof K K Koziol、Radosław Motyka、Krzysztof Z Walczak

  DOI：10.3762/bjoc.6.34

  日期：——

  uracils or N-9 Michael adducts of 6-chloropurine with methyl acrylate. The amines used were aliphatic/aromatic diamines, adenine, 5-substituted 1-(omega-aminoalkyl)uracils and 5'-amino-2',5'-dideoxythymidine. The title compounds may find application as antiprotozoal agents. Moreover, preliminary microscopy TEM studies of supramolecular behaviour showed that target molecules with bolaamphiphilic structures

  我们介绍了几种新型对称和不对称 α、ω-核碱基单-和双-酰胺共轭系统的合成和选定的物理化学性质，这些系统包含脂肪族、芳香族或糖类键。合成的最后阶段涉及带有羧基的亚单元与胺亚单元的缩合。发现 4-(4,6-二甲氧基-1,3,5-三嗪-2-基)-4-甲基吗啉氯化物 (DMT-MM) 是一种特别有效的缩合剂。含有羧基的亚基通过尿嘧啶的N-1迈克尔加合物或6-氯嘌呤的N-9迈克尔加合物与丙烯酸甲酯的酸水解获得。使用的胺是脂肪族/芳香族二胺、腺嘌呤、5-取代的1-(ω-氨基烷基)尿嘧啶和5'-氨基-2',5'-二脱氧胸苷。标题化合物可用作抗原生动物剂。此外，超分子行为的初步显微镜 TEM 研究表明，具有双亲结构的目标分子能够形成高度有序的组件，主要是纳米纤维。
• Studies on the chemistry of pyrimidine derivatives with dimethyldioxirane: synthesis, cytotoxic effect and antiviral activity of new 5,6-oxiranyl-5,6-dihydro and 5-hydroxy-5,6-dihydro-6-substituted uracil derivatives and pyrimidine nucleosides
  作者：Raffaele Saladino、Roberta Bernini、Claudia Crestini、Enrico Mincione、Alberto Bergamini、Stefano Marini、Anna Teresa Palamara

  DOI：10.1016/0040-4020(95)00380-q

  日期：1995.7

  The oxidation of uracil derivatives and pyrimidine nucleosides performed in CH2Cl2 with dimethyldioxirane afforded new 5,6-oxiranyl-5,6-dihydro and cis-/trans-5,6-dihvdroxv-5,6-dihydro-derivatives. When the oxidations were performed in the presence of methanol as nucleophile cis- and trans- 5-hydroxy-6-methoxy-5,6-dihydro derivatives were obtained in acceptable yields. Cis- and trans-1,3- dimethyl

  用二甲基二环氧乙烷在CH 2 Cl 2中进行尿嘧啶衍生物和嘧啶核苷的氧化，得到新的5，6-环氧乙烷基-5，6-二氢和顺式/反式-5，6-二羟基己酮-5，6-二氢衍生物。当在甲醇的存在下以亲核试剂的形式进行氧化时，以可接受的产率获得了顺式和反式5-羟基-6-甲氧基-5,6-二氢衍生物。通过1,3-二甲基-5,6-环氧乙烷基-5,6-二氢的亲核开环获得顺式和反式1,3-二甲基-5-羟基-6-烷基氨基-5,6-二氢尿嘧啶纯化形式的尿嘧啶。有趣的是，一些新的标题产品显示出低的细胞毒性和针对DNA和RNA病毒的选择性抗病毒活性。特别是化合物17b显示出对仙台病毒的强而有选择性的抑制作用，对单纯疱疹1病毒的影响较小。化合物17b在高浓度时也能够轻微抑制HIV-1病毒，但是在这种情况下，观察到了细胞毒性作用。
• Process for preparing triazole substituted azaindoleoxoacetic piperazine derivatives and novel salt forms produced therein
  申请人：Soundararajan Nachimuthu

  公开号：US20060293304A1

  公开（公告）日：2006-12-28

  A process is provided for preparing triazole substituted azaindoleoxoacetic piperazine derivative. Novel intermediates produced in the above process, and novel N-1 and amorphous forms of a 1,2,3-triazole substituted azaindoloxoacetic piperazine derivatives and processes for producing such novel forms are also provided.

  提供了一种制备三唑取代的氮杂吲哚氧乙酸哌嗪衍生物的过程。上述过程中产生的新型中间体，以及一种1,2,3-三唑取代的氮杂吲哚氧乙酸哌嗪衍生物的新型N-1和非晶形式，以及生产这种新型形式的过程也提供了。