2-[2-[[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxycarbonyloxy]ethyldisulfanyl]ethyl (3-azido-2-oxochromen-7-yl) carbonate | 1426657-94-4

• 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: 2-[2-[[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxycarbonyloxy]ethyldisulfanyl]ethyl (3-azido-2-oxochromen-7-yl) carbonate
• CAS: 1426657-94-4
• 化学式: C₂₄H₂₂F₂N₆O₁₁S₂
• 分子量: 672.601
• InChiKey: AOHNCIHKCHIUMO-YVWKXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  45
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  251
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  N-炔丙基生物素酰胺 、 2-[2-[[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxycarbonyloxy]ethyldisulfanyl]ethyl (3-azido-2-oxochromen-7-yl) carbonate 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 为溶剂， 反应 3.0h， 以25%的产率得到[3-[4-[[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]methyl]triazol-1-yl]-2-oxochromen-7-yl] 2-[2-[[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxycarbonyloxy]ethyldisulfanyl]ethyl carbonate
  参考文献：
  名称：

  Gemcitabine–Coumarin–Biotin Conjugates: A Target Specific Theranostic Anticancer Prodrug

  摘要：

  We present here, the design, synthesis, spectroscopic characterization, and in vitro biological assessment of a gemcitabine-coumarin-biotin conjugate (5). Probe 5 is a multifunctional molecule composed of a thiol-specific cleavable disulfide bond, a coumarin moiety as a fluorescent reporter, gemcitabine (GMC) as a model active drug, and biotin as a cancer-targeting unit. Upon addition of free thiols that are relatively abundant in tumor cells, disulfide bond cleavage occurs as well as active drug GMC release and concomitantly fluorescence intensity increases. Confocal microscopic experiments reveal that 5 is preferentially taken up by A549 cells rather than WI38 cells. Fluorescence-based colocalization studies using lysosome- and endoplasmic reticulum-selective dyes suggest that thiol-induced disulfide cleavage of 5 occur in the lysosome possibly via receptor-mediated endocytosis. The present drug delivery system is a new theranostic agent, wherein both a therapeutic effect and drug uptake can be readily monitored at the subcellular level by two photon fluorescence imaging.

  DOI：

  10.1021/ja401350x
• 作为产物：
  描述：

  在 吡啶 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 2-[2-[[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxycarbonyloxy]ethyldisulfanyl]ethyl (3-azido-2-oxochromen-7-yl) carbonate
  参考文献：
  名称：

  Gemcitabine–Coumarin–Biotin Conjugates: A Target Specific Theranostic Anticancer Prodrug

  摘要：

  We present here, the design, synthesis, spectroscopic characterization, and in vitro biological assessment of a gemcitabine-coumarin-biotin conjugate (5). Probe 5 is a multifunctional molecule composed of a thiol-specific cleavable disulfide bond, a coumarin moiety as a fluorescent reporter, gemcitabine (GMC) as a model active drug, and biotin as a cancer-targeting unit. Upon addition of free thiols that are relatively abundant in tumor cells, disulfide bond cleavage occurs as well as active drug GMC release and concomitantly fluorescence intensity increases. Confocal microscopic experiments reveal that 5 is preferentially taken up by A549 cells rather than WI38 cells. Fluorescence-based colocalization studies using lysosome- and endoplasmic reticulum-selective dyes suggest that thiol-induced disulfide cleavage of 5 occur in the lysosome possibly via receptor-mediated endocytosis. The present drug delivery system is a new theranostic agent, wherein both a therapeutic effect and drug uptake can be readily monitored at the subcellular level by two photon fluorescence imaging.

  DOI：

  10.1021/ja401350x