5-Amino-1-tert-butyl-3-(naphthalen-1-yloxymethyl)-1H-pyrazole-4-carbonitrile | 221243-79-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-Amino-1-tert-butyl-3-(naphthalen-1-yloxymethyl)-1H-pyrazole-4-carbonitrile
• 英文别名: 5-Amino-1-(tert-butyl)-3-((naphthalen-1-yloxy)methyl)-1H-pyrazole-4-carbonitrile；5-amino-1-tert-butyl-3-(naphthalen-1-yloxymethyl)pyrazole-4-carbonitrile
• CAS: 221243-79-4
• 化学式: C₁₉H₂₀N₄O
• 分子量: 320.394
• InChiKey: WICPNCODHLOFIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.82
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.86
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  5-Amino-1-tert-butyl-3-(naphthalen-1-yloxymethyl)-1H-pyrazole-4-carbonitrile 、 formamide 反应 12.0h， 生成 4-amino-1-tert-butyl-3-(1'-naphthoxymethyl)pyrazolo<3,4-d>pyrimidine
  参考文献：
  名称：

  Generation of Monospecific Nanomolar Tyrosine Kinase Inhibitors via a Chemical Genetic Approach

  摘要：

  Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the highly conserved fold of kinase catalytic domains. Through a combination of small molecule synthesis and protein mutagenesis, a highly potent (IC50 = 1.5 nM) and uniquely specific inhibitor (4-amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-d]pyrimidine) of a rationally engineered v-Src tyrosine kinase (Ile338Gly v-Src) has been identified. Both the potency and specificity of this compound surpass those of any known Src family tyrosine kinase inhibitors. The molecule strongly inhibits the engineered v-Src in whole cells but does not inhibit tyrosine phosphorylation in cells that express only wild-type tyrosine kinases. In addition, the inhibitor selectively disrupts transformation in cells that express the target v-Src. The structural degeneracy of kinase active sites should allow the same complementary inhibitor/protein design strategy to be widely applicable across this entire enzyme superfamily.

  DOI：

  10.1021/ja983267v
• 作为产物：
  描述：

  1-萘氧基乙酸 在 草酰氯 、 sodium hydride 、 碳酸氢钠 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 为溶剂， 反应 2.5h， 生成 5-Amino-1-tert-butyl-3-(naphthalen-1-yloxymethyl)-1H-pyrazole-4-carbonitrile
  参考文献：
  名称：

  Generation of Monospecific Nanomolar Tyrosine Kinase Inhibitors via a Chemical Genetic Approach

  摘要：

  Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the highly conserved fold of kinase catalytic domains. Through a combination of small molecule synthesis and protein mutagenesis, a highly potent (IC50 = 1.5 nM) and uniquely specific inhibitor (4-amino-1-tert-butyl-3-(1'-naphthyl)pyrazolo[3,4-d]pyrimidine) of a rationally engineered v-Src tyrosine kinase (Ile338Gly v-Src) has been identified. Both the potency and specificity of this compound surpass those of any known Src family tyrosine kinase inhibitors. The molecule strongly inhibits the engineered v-Src in whole cells but does not inhibit tyrosine phosphorylation in cells that express only wild-type tyrosine kinases. In addition, the inhibitor selectively disrupts transformation in cells that express the target v-Src. The structural degeneracy of kinase active sites should allow the same complementary inhibitor/protein design strategy to be widely applicable across this entire enzyme superfamily.

  DOI：

  10.1021/ja983267v