1-[(2R,5S)-5-(methoxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 1-[(2R,5S)-5-(methoxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
• 英文别名: me-d4T；kamuvudine 1；1-[(2R,5S)-5-(methoxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₁₁H₁₄N₂O₄
• 分子量: 238.243
• InChiKey: WVLFJUZGAVGKEB-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3-O-isopropylidene-5-O-methyl-D-ribofuranose 在 4-二甲氨基吡啶 、 三氟甲磺酸三甲基硅酯 、 三乙胺 、 三甲氧基磷 作用下， 以 甲醇 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 7.0h， 生成 1-[(2R,5S)-5-(methoxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR TREATING RETINAL DEGRADATION
  [FR] COMPOSITIONS ET MÉTHODES POUR LE TRAITEMENT DE DÉGRADATIONS DE LA RÉTINE

  摘要：

  本公开涉及用于治疗视网膜损伤和/或视网膜降解/视网膜退化的化合物、组合物和方法，用于通过与细胞相关的Alu RNA抑制炎症小体的激活，用于减少细胞对ATP诱导的渗透性，用于减少细胞中线粒体活性氧物质的量，以及用于减少细胞中线粒体活性氧物质的量。本公开还涉及用于保护RPE细胞和/或用于治疗与视网膜损伤和/或降解相关的疾病的化合物、组合物和方法，包括但不限于干性老年性黄斑变性（AMD）和湿性AMD、阿尔茨海默病、各种形式的关节炎、动脉粥样硬化、糖尿病、慢性阻塞性肺病、炎症性肠病和杜兴氏肌肉萎缩症的预防和治疗。

  公开号：

  WO2016138425A1

文献信息

• NUCLEOSIDE KINASE BYPASS COMPOSITIONS AND METHODS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20150315221A1

  公开（公告）日：2015-11-05

  The present invention relates to disulfide masked prodrug compounds, compositions and methods that are amenable to bioactivation by a reducing agent such as glutathione. Such disulfide based compounds, compositions, and methods can be useful, for example, in providing novel prodrugs for use as therapeutics.

  本发明涉及一种二硫化物掩蔽的前药化合物、组合物和方法，这些化合物、组合物和方法可通过还原剂如谷胱甘肽进行生物活化。这种基于二硫化物的化合物、组合物和方法可以用于提供新型前药，例如用作治疗药物。
• 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。
• COMPOSITIONS AND METHODS FOR TREATING RETINAL DEGRADATION
  申请人：University Of Kentucky Research Foundation

  公开号：EP3261644B1

  公开（公告）日：2021-06-02
• Compositions and Methods for Treating Retinal Degradation
  申请人：University of Kentucky Research Foundation

  公开号：US20210220359A1

  公开（公告）日：2021-07-22

  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.