[(2R,3R,4R,5R)-5-[4-amino-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-hydroxy-4-prop-2-ynoxyoxolan-2-yl]methyl ethenesulfonate | 1414782-66-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: [(2R,3R,4R,5R)-5-[4-amino-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-hydroxy-4-prop-2-ynoxyoxolan-2-yl]methyl ethenesulfonate
• CAS: 1414782-66-3
• 化学式: C₂₃H₂₄N₄O₆S
• 分子量: 484.533
• InChiKey: JSIBVUYNTRLYHF-ZDXOVATRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-O-<(1,1-dimethylethyl)dimethylsilyl>-2,3-O-(1-methylethylidene)-β-D-ribofuranosyl chloride 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 三(3,6-二氧杂庚基)胺 、 四丁基氟化铵 、 四丁基碘化铵 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 6.0h， 生成 [(2R,3R,4R,5R)-5-[4-amino-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-hydroxy-4-prop-2-ynoxyoxolan-2-yl]methyl ethenesulfonate
  参考文献：
  名称：

  Selective Targeting of Distinct Active Site Nucleophiles by Irreversible Src-Family Kinase Inhibitors

  摘要：

  Src-family tyrosine kinases play pivotal roles in human physiology and disease, and several drugs that target members of this family are in clinical use. None of these drugs appear to discriminate among closely related kinases. However, assessing their selectivity toward endogenous kinases in living cells remains a significant challenge. Here, we report the design of two Src-directed chemical probes, each consisting of a nucleoside scaffold with a 5'-electrophile. A 5'-fluorosulfonylbenzoate (1) reacts with the conserved catalytic lysine (Lys295) and shows little discrimination among related kinases. By contrast, a 5'-vinylsulfonate (2) reacts with a poorly conserved, proximal cysteine (Cys277) found in three Src-family and six unrelated kinases. Both 1 and 2 bear an alkyne tag and efficiently label their respective endogenous kinase targets in intact cells. Using 1 as a competitive probe, we determined the extent to which ponatinib, a clinical Bcr-Abl inhibitor, targets Src-family kinases. Remarkably, while ponatinib had little effect on endogenous Fyn or Src, it potently blocked the critical T-cell kinase, Lck. Probes 1 and 2 thus enable competitive profiling versus distinct kinase subsets in living cells.

  DOI：

  10.1021/ja310659j