1-(tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)-5-iodouracil | 149312-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)-5-iodouracil
• 英文别名: 1,5-Anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol；1',5'-Anhydro-2',3'-dideoxy-2'-(5-iodouracil-1-YL)-D-ababino-hexitol；1-[(3S,5S,6R)-5-hydroxy-6-(hydroxymethyl)oxan-3-yl]-5-iodopyrimidine-2,4-dione
• CAS: 149312-03-8
• 化学式: C₁₀H₁₃IN₂O₅
• 分子量: 368.128
• InChiKey: PJDQVZSBWDEYOF-APQOSEDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)-5-iodouracil 在 吡啶 、 三氯氧磷 作用下， 反应 74.0h， 生成 Acetic acid (2R,3S,5S)-2-acetoxymethyl-5-(5-iodo-2-oxo-4-[1,2,4]triazol-1-yl-2H-pyrimidin-1-yl)-tetrahydro-pyran-3-yl ester
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Structure Analysis of a Series of New 1,5-Anhydrohexitol Nucleosides

  摘要：

  In view of the selective anti-HSV activity of 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol,(1) a series of novel 1,5-anhydrohexitol nucleosides were synthesized and evaluated for their inhibitory activity against several viruses. The 5-iodouracil 3 and the 5-ethyluracil 4 derivatives are highly selective TK-dependent inhibitors of HSV-1 and HSV-2. Broad anti-herpes virus activity was noticed for 5-fluorocytosine 6 and 2,6-diaminopurine 10 analogues. From a transport study of 3, using the thymidine influx competition method, one can conclude that intracellular uptake of this compound most probably occurs by passive diffusion. X-ray analysis of compounds 3 and 9 showed that the heterocyclic base of 1,5-anhydrohexitol pyrimidine and purine is placed in the axial position and that the sugar ring adopts a slightly distorted chair conformation.

  DOI：

  10.1021/jm00005a010
• 作为产物：
  描述：

  1-deoxy-D-glucose tetraacetate 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium methylate 、 二正丁基氧化锡 、 溶剂黄146 、 zinc(II) chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 91.0h， 生成 1-(tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)-5-iodouracil
  参考文献：
  名称：

  1,5-脱水己糖醇核苷的合成及其抗疱疹病毒活性。

  摘要：

  描述了1，5-脱水己糖醇核苷的合成。这些核苷类似物是通过在甲苯磺酰脲（Mitsunobu）条件下用甲苯磺酸酯10使杂环碱烷基化或通过用醇12使碱烷基化而获得的。评价化合物的抗病毒和细胞抑制活性。对于1,5-脱水-2,3-二脱氧-2-（5-碘尿嘧啶-1-基）-D注意到对1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）具有高度选择性。 -阿拉伯糖基己糖醇4b的浓度为0.07微克/毫升。此活性必须取决于病毒编码的胸苷激酶（TK）的特定磷酸化作用，因为化合物4b对HSV-1的TK缺陷型突变体无活性。相应的胞嘧啶4c和鸟嘌呤4e类似物对HSV-1，HSV-2和其他疱疹病毒（例如巨细胞病毒，水痘-带状疱疹病毒）浓度远低于细胞毒性阈值（分别为2和20微克/ mL）。在这些浓度下，化合物4c和4e还被证明对人类T细胞（即MT-4，CEM，MOLT-4）的生长具有抑制作用。

  DOI：

  10.1021/jm00066a013

文献信息

• 5-Substituted Pyrimidines with a 1,5-Anhydro-2,3-dideoxy-<scp>d</scp>-<i>arabino</i>-hexitol Moiety at N-1:  Synthesis, Antiviral Activity, Conformational Analysis, and Interaction with Viral Thymidine Kinase
  作者：Tomasz Ostrowski、Berthold Wroblowski、Roger Busson、Jozef Rozenski、Erik De Clercq、Matthew S. Bennett、John N. Champness、William C. Summers、Mark R. Sanderson、Piet Herdewijn

  DOI：10.1021/jm980287z

  日期：1998.10.1

  A new series of anhydrohexitol nucleosides are described. These compounds have a pyrimidine base moiety substituted in the 5-position with a chloro (1b), trifluoromethyl (1c), vinyl (1d), 2-thienyl (1e), ethynyl (1f) or propynyl (1g) substituent. The vinyl, propynyl, and, in particular, the 5-trifluoromethyl analogue showed potent activity against herpes simplex virus (HSV), 1c with a selectivity index

  描述了一系列新的脱水己糖醇核苷。这些化合物具有在5位上被氯（1b），三氟甲基（1c），乙烯基（1d），2-噻吩基（1e），乙炔基（1f）或丙炔基（1g）取代基取代的嘧啶碱基部分。乙烯基，丙炔基，尤其是5-三氟甲基类似物显示出对单纯疱疹病毒（HSV）的有效活性，其1c对HSV-1的选择性指数> 16000，对HSV-2的选择性指数> 1000。使用计算方法对脱水己糖醇核苷进行构象分析表明，这些核苷在C1和1C形式之间平衡存在，其DeltaE为5.9 kJ / mol。当脱水己糖醇核苷与HSV-1胸苷激酶共结晶时，它采用1C构象，这与仅在小分子中发现的构象相反。酵素
• Nucleotide analogs with six membered rings
  申请人：Roche Diagnostics GmbH

  公开号：EP1466919A1

  公开（公告）日：2004-10-13

  The present invention is related to compounds comprising six-membered rings capable of being incorporated into nucleic acids. Particularly, the six membered ring is a derivative of cyclohexane, cyclohexene, tetrahydropyran, tetrahydrothiopyran or piperidine. These compounds may be used to build up oligomeric compounds. The invention is further related to uses of these oligomeric compounds for hybridization and as probes. In addition, methods for the detection of nucleic acids are provided wherein the oligomeric compounds are used.

  本发明涉及包含能够被并入核酸的六元环的化合物。特别是，这个六元环是环己烷、环己烯、四氢吡喃、四氢硫吡喃或哌啶的衍生物。这些化合物可以用于构建寡聚合物化合物。该发明还涉及这些寡聚合物化合物用于杂交和作为探针的用途。此外，提供了检测核酸的方法，其中使用了这些寡聚合物化合物。
• Nucleotide analogs with six-membered rings
  申请人：Bergmann Frank

  公开号：US20050004078A1

  公开（公告）日：2005-01-06

  The present invention is related to compounds comprising six-membered rings capable of being incorporated into nucleic acids. Particularly, the six-membered ring is a derivative of cyclohexane, cyclohexene, tetrahydropyran, tetrahydrothiopyran or piperidine. These compounds may be used to build up oligomeric compounds. The invention is further related to uses of these oligomeric compounds for hybridization and as probes. In addition, methods for the detection of nucleic acids are provided wherein the oligomeric compounds are used.

  本发明涉及包含六元环的化合物，可被合并到核酸中。特别地，这个六元环是环己烷、环己烯、四氢吡喃、四氢噻吩或哌啶的衍生物。这些化合物可用于构建寡聚化合物。该发明还涉及这些寡聚化合物用于杂交和作为探针的用途。此外，提供了用于检测核酸的方法，其中使用了这些寡聚化合物。
• NUCLEOTIDE ANALOGS WITH SIX-MEMBERED RINGS
  申请人：Bergmann Frank

  公开号：US20080038745A1

  公开（公告）日：2008-02-14

  The present invention is related to compounds comprising six-membered rings capable of being incorporated into nucleic acids. Particularly, the six-membered ring is a derivative of cyclohexane, cyclohexene, tetrahydropyran, tetrahydrothiopyran or piperidine. These compounds may be used to build up oligomeric compounds. The invention is further related to uses of these oligomeric compounds for hybridization and as probes. In addition, methods for the detection of nucleic acids are provided wherein the oligomeric compounds are used.

  本发明涉及包含六元环的化合物，这些化合物能够被合并到核酸中。特别地，这个六元环是环己烷、环己烯、四氢吡喃、四氢噻吩或哌啶的衍生物。这些化合物可用于建立寡聚物化合物。此外，本发明还涉及使用这些寡聚物化合物进行杂交和作为探针的用途。此外，提供了使用寡聚物化合物进行核酸检测的方法。
• Antiviral tetrahydropyrans
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0608809A1

  公开（公告）日：1994-08-03

  Compounds of the formula including pharmaceutically acceptable salts are useful as antiviral agents.

  式中的化合物包括药学上可接受的盐类可用作抗病毒剂。