5-Amino-3-benzo[1,3]dioxol-5-yl-1-tert-butyl-1H-pyrazole-4-carbonitrile | 221243-71-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 5-Amino-3-benzo[1,3]dioxol-5-yl-1-tert-butyl-1H-pyrazole-4-carbonitrile
• CAS: 221243-71-6
• 化学式: C₁₅H₁₆N₄O₂
• 分子量: 284.318
• InChiKey: DNQRZQBRSWRRCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.49
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  86.09
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5-Amino-3-benzo[1,3]dioxol-5-yl-1-tert-butyl-1H-pyrazole-4-carbonitrile 、 formamide 反应 12.0h， 生成 4-amino-1-tert-butyl-3-piperonylpyrazolo<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：

  胡椒酸酰氯 在 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 3.0h， 生成 5-Amino-3-benzo[1,3]dioxol-5-yl-1-tert-butyl-1H-pyrazole-4-carbonitrile
  参考文献：
  名称：

  Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii

  摘要：

  Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.

  DOI：

  10.1021/jm4001314