(2-methylen-5(R)-(thymin-1-yl))-2,5-dihydrofuran | 52523-38-3

• 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: (2-methylen-5(R)-(thymin-1-yl))-2,5-dihydrofuran
• 英文别名: 5-Methyl-1-[(2R)-5-methylidene-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione；5-methyl-1-[(2R)-5-methylidene-2H-furan-2-yl]pyrimidine-2,4-dione
• CAS: 52523-38-3
• 化学式: C₁₀H₁₀N₂O₃
• 分子量: 206.201
• InChiKey: UFACXRIGIONWIV-MRVPVSSYSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  (2-methylen-5(R)-(thymin-1-yl))-2,5-dihydrofuran 在 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 以95%的产率得到2-methyl-5-(thymin-1-yl)furan
  参考文献：
  名称：

  Independent Synthesis and Fate Studies of Impurities in Process Intermediates of the Anti-AIDS Drug d4T

  摘要：

  Impurities in isolated intermediates in a process to prepare d4T were identified, independently synthesized, and then taken through the process to determine their ultimate fate. Some of the products from these fate studies were also independently synthesized and used in the validation of impurity assay methods.

  DOI：

  10.1021/op970126p
• 作为产物：
  描述：

  司他夫定 在 甲醇 、 sodium methylate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 生成 (2-methylen-5(R)-(thymin-1-yl))-2,5-dihydrofuran
  参考文献：
  名称：

  Some reactions of (5R)-2-methylene-5-(thymin-1-yl)-2,5-dihydrofuran

  摘要：

  The title compound 4 was quantitatively converted into the isomeric furan derivative 5 under relatively mild acidic conditions; when compound 4 was treated with 3-chloroperbenzoic acid in dichloromethane and sodium hypochlorite in aqueous dioxane, compounds 9 and 11, respectively, were obtained. Both compounds were isolated in 48% yield.

  DOI：

  10.1039/p19920000441

文献信息

• Electrophile-promoted addition of hydroxymethylphosphonate to 4′,5′-didehydronucleosides: a way to novel isosteric analogues of 5′-nucleotides
  作者：Zdeněk Točík、Ivana Dvořáková、Radek Liboska、Miloš Buděšínský、Milena Masojídková、Ivan Rosenberg

  DOI：10.1016/j.tet.2007.03.059

  日期：2007.5

  addition of dialkyl-hydroxymethylphosphonate to the protected 4′,5′-didehydronucleosides resulted in an epimeric mixture of 4′-dialkylphosphonomethoxy derivatives of 2′,5′-dideoxynucleosides, novel analogues of 2′-deoxynucleoside 5′-monophosphates. Several types of electrophiles (pyridinium tosylate, NIS, NBS, MCPBA and others) were evaluated in addition reactions with 4′,5′-didehydrothymidine. Out

  亲电子促进的将二烷基羟甲基膦酸酯加到受保护的4'，5'-didehydronucleosides上，生成2'，5'-dideoxynucleosides的4'-di烷基膦酰基甲氧基衍生物的差向异构体混合物，这是2'-deoxynucleoside 5'-monophosphates的新类似物。在与4'，5'-二氢胸苷的加成反应中评估了几种类型的亲电试剂（甲苯磺酸吡啶鎓，NIS，NBS，MCPBA等）。从中发现，甲苯磺酸吡啶鎓在这些转化中具有实际用途。它的使用导致了一系列常见2'-脱氧核苷的4'-膦酰基甲氧基衍生物的制备。在生物学筛选中，这些游离膦酸没有发挥明显的细胞抑制或抗病毒活性。
• COMPOSITIONS AND METHODS FOR TREATING RETINAL DEGRADATION
  申请人：University of Kentucky Research Foundation

  公开号：EP3858826A1

  公开（公告）日：2021-08-04

  The present disclosure relates to compounds, compositions, and methods useful for treating retinal damage and/or retinal degradation / retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to compounds, compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.

  本公开涉及用于治疗视网膜损伤和/或视网膜退化/视网膜变性的化合物、组合物和方法，用于抑制与细胞相关的Alu RNA激活炎性体，用于降低ATP诱导的细胞通透性，用于降低细胞中线粒体活性氧的量，以及用于降低细胞中线粒体活性氧的量。本公开进一步涉及用于保护 RPE 细胞和/或用于治疗（包括预防性和治疗性治疗）与视网膜损伤和/或退化相关的病症的化合物、组合物和方法，这些病症包括但不限于干性年龄相关性黄斑变性（AMD）和湿性 AMD、老年痴呆症、各种形式的关节炎、动脉粥样硬化、糖尿病、慢性阻塞性肺病、炎症性肠病和杜氏肌营养不良症。
• Compositions and methods for treating retinal degradation
  申请人：University of Kentucky Research Foundation

  公开号：US10294220B2

  公开（公告）日：2019-05-21

  The present disclosure relates to nucleosides, such as compositions, and methods useful for treating retinal damage and/or retinal degradation/retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to nucleosides, such as compositions, and methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.

  本公开涉及核苷类化合物，如 组合物，以及用于治疗视网膜损伤和/或视网膜退化/视网膜变性、抑制与细胞相关的 Alu RNA 的炎性体活化、降低 ATP 诱导的细胞通透性、减少细胞中线粒体活性氧的量的方法。本公开进一步涉及核苷，例如 用于保护 RPE 细胞和/或治疗（包括预防性和治疗性治疗）与视网膜损伤和/或退化有关的病症的组合物和方法，这些病症包括但不限于干性老年黄斑变性（AMD）和湿性 AMD、老年痴呆症、各种形式的关节炎、动脉粥样硬化、糖尿病、慢性阻塞性肺病、炎症性肠病和杜氏肌营养不良症。
• Inflammasome inhibition for the treatment of Parkinson's disease, Alzheimer's disease and multiple sclerosis
  申请人：University of Kentucky Research Foundation

  公开号：US11219623B2

  公开（公告）日：2022-01-11

  The present disclosure relates to modified nucleoside reverse transcriptase inhibitors (NRTIs), such as and compositions thereof, as well as methods useful for treating retinal damage and/or retinal degradation/retinal degeneration, for inhibiting inflammasome activation by Alu RNA associated with a cell, for reducing ATP-induced permeability of a cell, for reducing an amount of mitochondrial reactive oxygen species in a cell, and for reducing an amount of mitochondrial reactive oxygen species in a cell. The present disclosure further relates to modified NRTIs, such as and compositions thereof, as well as methods for use in protecting an RPE cell and/or for treating, including prophylactic and therapeutic treatment, of conditions associated with retinal damage and/or degradation including, but not limited to, dry age related macular degeneration (AMD) and wet AMD, Alzheimer disease, various forms of arthritis, atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, inflammatory bowel disease, and Duchenne muscular dystrophy.

  本公开涉及改良的核苷类逆转录酶抑制剂（NRTIs），如 及其组合物，以及用于治疗视网膜损伤和/或视网膜退化/视网膜变性、抑制与细胞相关的Alu RNA激活炎性体、降低ATP诱导的细胞通透性、减少细胞中线粒体活性氧的量以及减少细胞中线粒体活性氧的量的方法。本公开进一步涉及改良的 NRTIs，例如 及其组合物，以及用于保护 RPE 细胞和/或治疗（包括预防性和治疗性治疗）与视网膜损伤和/或退化相关的病症的方法，这些病症包括但不限于干性老年黄斑变性（AMD）和湿性 AMD、老年痴呆症、各种形式的关节炎、动脉粥样硬化、糖尿病、慢性阻塞性肺病、炎症性肠病和杜氏肌营养不良症。
• Nucleoside sultones: synthons for the preparation of novel nucleotide analogs. 1. Synthesis and ring-opening reactions
  作者：Peter A. Crooks、Robert C. Reynolds、Joseph A. Maddry、Anita Rathore、M. Shamim Akhtar、John A. Montgomery、John A. Secrist

  DOI：10.1021/jo00036a014

  日期：1992.5

  Treatment of either the 5'-O-tosyl or the 5'-O-mesyl derivative of 3'-O-mesylthymidine with lithium acetylide-ethylenediamine complex in DMSO affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-l-(3,4-dihydro-5-methyl-2, 4-dioxo-1(2H)-pyrimidinyl)-beta-D-erythro-hexofuranuronosulfonic acid (2). Similarly, the 5'-O-tosyl or 5'-O-mesyl derivative of 1-(2-deoxy-3-O-mesyl-beta-D-threo-pentofuranosyl)thymine affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-1-(3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)-beta-D-threo-hexofuranurononsulfonic acid (5). Sultone 5 reacts with a variety of nucleophiles to afford good yields of the corresponding 3'-substituted sulfonate salts (6, 7, 9, and 10) and, in some cases, the unsaturated nucleoside 8. Sultone 2 was generally much less susceptible to ring opening by nucleophiles. However, in the presence of base, nucleophilic substitution with azide ion did proceed via the intermediate anhydronucleoside, 11, to afford 6. Reaction of 2 with EtOH-NaOH afforded a 1:1 mixture of the epimeric 3'-hydroxy compounds 9 and 12. The above sulfonate salts represent interesting new isosteres of nucleoside 5'-O-phosphates.