5-(4-trans-amino-cyclohexylamino)-7-isopropylaminopyrazole[1,5-a]pyrimidine-3-carbonitrile | 1048675-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 5-(4-trans-amino-cyclohexylamino)-7-isopropylaminopyrazole[1,5-a]pyrimidine-3-carbonitrile
• CAS: 1048675-57-5
• 化学式: C₁₆H₂₃N₇
• 分子量: 313.406
• InChiKey: FOESVLPZMGVWBM-JOCQHMNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  104.06
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  5-chloro-7-isopropylaminopyrazolo[1,5-a]pyrimidine-3-carbonitrile 、 trans-1,4-Diaminocyclohexane 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 5-(4-trans-amino-cyclohexylamino)-7-isopropylaminopyrazole[1,5-a]pyrimidine-3-carbonitrile
  参考文献：
  名称：

  Identification of N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design

  摘要：

  The application of fragment-based screening techniques to cyclin dependent kinase 2 (CDK2) identified multiple (>30) efficient, synthetically tractable small molecule hits for further optimization. Structure-based design approaches led to the identification of multiple lead series, which retained the key interactions of the initial binding fragments and additionally explored other areas of the ATP binding site. The majority of this paper details the structure-guided optimization of indazole (6) using information gained from multiple ligand-CDK2 cocrystal structures. Identification of key binding features for this class of compounds resulted in a series of molecules with low nM affinity for CDK2. Optimisation of cellular activity and characterization of pharmacokinetic properties led to the identification of 33 (AT7519), which is currently being evaluated in clinical trials for the treatment of human cancers.

  DOI：

  10.1021/jm800382h