1-(3,5-O-di(tetrahydropyran-2-yl)-β-D-arabinofuranosyl)thymine | 351523-08-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(3,5-O-di(tetrahydropyran-2-yl)-β-D-arabinofuranosyl)thymine
• 英文别名: 1-[(2R,3S,4S,5R)-3-hydroxy-4-(oxan-2-yloxy)-5-[(oxan-2-yloxy)methyl]oxolan-2-yl]-5-methyl-3H-pyrimidine-2,4-dione；3',5'-O-Bis-(tetrahydropyranyl)-5-methyl-1-β-D-arabinofuranosyluracil；1-[(2R,3S,4S,5R)-3-hydroxy-4-(oxan-2-yloxy)-5-(oxan-2-yloxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 351523-08-5
• 化学式: C₂₀H₃₀N₂O₈
• 分子量: 426.467
• InChiKey: DRGUHZIBJATQFP-UQGQJXCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(3,5-O-di(tetrahydropyran-2-yl)-β-D-arabinofuranosyl)thymine 在 4-二甲氨基吡啶 四丁基氟化铵 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 tert-butyl 5-methyl-2,6-dioxo-3-((2R,3S,4R,5R)-4-(tetrahydro-2H-pyran-2-yloxy)-5-((tetrahydro-2H-pyran-2-yloxy)methyl)-3-(2-(tosyloxy)ethoxy)tetrahydrofuran-2-yl)-2,3-dihydropyrimidine-1(6H)-carboxylate
  参考文献：
  名称：

  WO2008/109080

  摘要：

  公开号：
• 作为产物：
  描述：

  2,2'-O-脱水-5-甲基尿嘧啶核苷 在 氢氧化钾 、 对甲苯磺酸 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 1-(3,5-O-di(tetrahydropyran-2-yl)-β-D-arabinofuranosyl)thymine
  参考文献：
  名称：

  Design, Synthesis and Enzymatic Activity of Highly Selective Human Mitochondrial Thymidine Kinase Inhibitors

  摘要：

  Highly selective arabinofuranosyl nucleosides, which inhibit the mitochondrial thymidine kinase (TK-2) without affecting the closely related herpes simplex virus type 1 thymidine kinase (HSV-1 TK), varicella-zoster virus thymidine kinase (VZV-TK), cytosolic thymidine kinase (TK-1) or the multifunctional Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK), have been obtained. SAR studies indicate a close relation between the length of the substituent at the 2' position of the arabinofuranosyl moiety and the inhibitory activity. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00207-4

文献信息

• SYNTHESIS AND IN VITRO ANTI-HCV ACTIVITY OF β-D- and L-2′-DEOXY-2′-FLUORORIBONUCLEOSIDES
  作者：Junxing Shi、Jinfa Du、Tianwei Ma、Krzysztof Pankiewicz、Steven E. Patterson、Abdalla E. A. Hassan、Phillip M. Tharnish、Tamara R. McBrayer、Stefania Lostia、Lieven J. Stuyver、Kyoichi A. Watanabe、Chung K. Chu、Raymond F. Schinazi、Michael J. Otto

  DOI：10.1081/ncn-200059224

  日期：2005.4.1

  5-fluoro compounds, namely β-D-2′-deoxy-2′,5-difluorocytidine (5), had anti-HCV activity in the subgenomic HCV replicon cell line, and inhibitory activity against ribosomal RNA. As β-D-N4-hydroxycytidine (NHC) had previously shown potent anti-HCV activity, the two functionalities of the N4-hydroxyl and the 2′-fluoro were combined into one molecule, yielding β-D-2′-deoxy-2′-fluoro-N4-hydroxycytidine (12)

  基于 β-D-2'-deoxy-2'-fluorocytidine 作为一种有效的抗丙型肝炎病毒 (HCV) 药物的发现，一系列 β-D- 和 l-2'-deoxy-2'-fluororibonucleosides合成了在 5 和/或 4 位进行修饰的 HCV，并评估了它们对 HCV 和牛病毒性腹泻病毒 (BVDV) 的体外活性。2'-氟基团的引入是通过用氟化氢-吡啶或氟化钾对 2,2'-脱水核苷进行氟化，或用 DAST 对阿拉伯核苷进行氟化来实现的。在合成的 27 个类似物中，只有 5-氟化合物，即 β-D-2'-deoxy-2',5-difluorocytidine (5) 在亚基因组 HCV 复制子细胞系中具有抗 HCV 活性，并且对核糖体 RNA。由于 β-D-N4-羟基胞苷 (NHC) 先前已显示出有效的抗 HCV 活性，N4-羟基和 2'-氟的两个官能团结合成一个分子，产生 β
• Novel selective human mitochondrial kinase inhibitors: Design, synthesis and enzymatic activity
  作者：Nunzia Ciliberti、Stefano Manfredini、Angela Angusti、Elisa Durini、Nicola Solaroli、Silvia Vertuani、Lisa Buzzoni、Maria Cruz Bonache、Efrat Ben-Shalom、Anna Karlsson、Ann Saada、Jan Balzarini

  DOI：10.1016/j.bmc.2007.01.049

  日期：2007.4

  Selective and effective TK2 inhibitors can be obtained by introduction of bulky lipophilic chains (acyl or alkyl entities) at the 2' position of araT and BVaraU, nucleoside analogues naturally endowed with a low TK2 affinity. These derivatives showed a competitive inhibitory activity against TK2 in micromolar range. BVaraU nucleoside analogues, modified on the 2'-O-acyl chain with a terminal N-Boc amino-group, conserved or increased the inhibitory activity against TK2 (71 and 7m IC50: 6.4 and 3.8 mu M, respectively). The substitution of an ester for a carboxamide moiety at the 2' position of araT afforded a consistent reduction of the inhibitory activity (25, IC50: 480 mu M). On the contrary, modifications at 2'-OH position of araC and araG, have provided inactive derivatives against TK2 and dGK, respectively. The biological activity of a representative compound, 2'-O-decanoyl-BVaraU, was also investigated in normal human fibroblasts and was found to impair mitochondrial function due to TK2 inhibition. (c) 2007 Published by Elsevier Ltd.
• Nucleoside based proliferation imaging markers
  申请人：Kolb Hartmuth C.

  公开号：US20090016958A1

  公开（公告）日：2009-01-15

  Disclosed herein are novel radiolabeled nucleosides and methods for detecting cellular proliferation in a mammal, the method comprising administrating an effective amount of a radiolabeled nucleoside; the method comprising: a) administering to the mammal a diagnostically effective amount of the nucleoside to the mammal; b) allowing the nucleoside to distribute into the effective tissue; and c) imaging the tissue, wherein an increase in binding of the compound to tissue compared to a normal control level of binding indicates that the mammal is suffering from a disease involving cellular proliferation.
• [EN] COMPOUNDS AND METHODS FOR TREATING DISEASE<br/>[FR] COMPOSÉS ET MÉTHODES POUR TRAITER UNE MALADIE
  申请人：[en]ROME THERAPEUTICS, INC.

  公开号：WO2023178133A1

  公开（公告）日：2023-09-21

  The invention provides compounds, compositions and methods for treating medical disorders, such as cancer, an autoimmune disorder, and/or a neurological disorder, and inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase using a compound according to Formula I or a pharmaceutically acceptable salt thereof, or a related compound provided herein.
• WO2008/109080
  申请人：——

  公开号：——

  公开（公告）日：——