4-(3-tert-butyl-1H-pyrazol-4-yl)-2-methylsulfanyl-pyrimidine | 1256963-10-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-(3-tert-butyl-1H-pyrazol-4-yl)-2-methylsulfanyl-pyrimidine
• 英文别名: 4-(5-tert-butyl-1H-pyrazol-4-yl)-2-methylsulfanylpyrimidine
• CAS: 1256963-10-6
• 化学式: C₁₂H₁₆N₄S
• 分子量: 248.352
• InChiKey: QGCKDOFLLHPCNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-tert-butyl-1H-pyrazol-4-yl)-2-methylsulfanyl-pyrimidine 在 oxone 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 4-(3-tert-butyl-1H-pyrazol-4-yl)-2-methanesulfonyl-pyrimidine
  参考文献：
  名称：

  4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6

  摘要：

  Identification and structure-guided optimization of a series of 4-(pyrazol-4-yl)-pyrimidines as selective CDK 4/6 inhibitors is reported herein. Several potency and selectivity determinants were established based on the X-ray crystallographic analysis of representative compounds bound to monomeric CDK 6. Significant selectivity for CDK4/6 over CDK 1 and CDK2 was demonstrated with several compounds in both enzymatic and cellular assays.

  DOI：

  10.1021/jm100571n
• 作为产物：
  描述：

  三甲基乙酸甲酯 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 130.0h， 生成 4-(3-tert-butyl-1H-pyrazol-4-yl)-2-methylsulfanyl-pyrimidine
  参考文献：
  名称：

  Lead Optimization toward Proof-of-Concept Tools for Huntington’s Disease within a 4-(1H-Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors

  摘要：

  Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.

  DOI：

  10.1021/jm5013598