4-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine | 1158908-48-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine
• 英文别名: 4-[5-(4-chlorophenyl)-1H-pyrazol-4-yl]-2-methylsulfanylpyrimidine
• CAS: 1158908-48-5
• 化学式: C₁₄H₁₁ClN₄S
• 分子量: 302.787
• InChiKey: XTIJIVMZWPREAU-UHFFFAOYSA-N

物化性质

• 沸点：
  512.0±45.0 °C(predicted)
• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 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-(4-chlorophenyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine 在 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.5h， 生成 trans-(4-(4-(3-chlorophenyl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)cyclohexanol
  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
• 作为产物：
  描述：

  在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 4-(3-(4-chlorophenyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine
  参考文献：
  名称：

  Synthesis and SAR of 4-substituted-2-aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors

  摘要：

  The development of a series of novel 4-substituted-2-aminopyrimidines as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, and the in vitro inhibitory value for a c-Jun cellular assay are discussed. Optimization of microsomal clearance led to the identification of 9c, whose kinase selectivity is reported. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.023

文献信息

• Chemically enabled synthesis of 2-amino-4-heteroarylpyrimidines
  作者：Paul S. Humphries、Quyen-Quyen T. Do、David M. Wilhite

  DOI：10.1016/j.tetlet.2009.03.073

  日期：2009.5

  2-Amino-4-heteroarylpyrimidines were initially synthesized by microwave-induced SNAr reactions of primary alkyl amines and 2-methylsulfonylpyrimidines or 2-chloropyrimidines. Following this methodology, pendant piperidine functionality was elaborated utilizing silica-bound reagents in microwave-assisted reductive amination and amide bond formation protocols. These methods proved to be versatile, efficient, and amenable to parallel synthesis. (C) 2009 Elsevier Ltd. All rights reserved.