[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 | 1426657-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: [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
• CAS: 1426657-99-9
• 化学式: C₃₇H₄₁F₂N₉O₁₃S₃
• 分子量: 953.98
• InChiKey: OZRQDXSHFNJFNI-VHNVIZNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  64
• 可旋转键数：
  23
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  362
• 氢给体数：
  5
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  [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 在 谷胱甘肽 作用下， 反应 1.0h， 生成 N-((1-(7-hydroxy-2-oxo-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide 、 吉西他滨
  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：

  D-生物素 在 copper(ll) sulfate pentahydrate 、 1-羟基苯并三唑 、 sodium ascorbate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 生成 [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