5-chloro-6-methyl-2-(methylthio)pyrimidin-4(3H)-one | 6328-59-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-chloro-6-methyl-2-(methylthio)pyrimidin-4(3H)-one
• 英文别名: 5-chloro-6-methyl-2-methylsulfanyl-3H-pyrimidin-4-one；5-Chlor-6-methyl-2-methylmercapto-3H-pyrimidin-4-on；5-Chloro-6-methyl-2-(methylsulfanyl)pyrimidin-4(1h)-one；5-chloro-4-methyl-2-methylsulfanyl-1H-pyrimidin-6-one
• CAS: 6328-59-2
• 化学式: C₆H₇ClN₂OS
• 分子量: 190.653
• InChiKey: VJVKERKTPVPFEJ-UHFFFAOYSA-N

物化性质

• 熔点：
  260-261 °C(Solv: isopropanol (67-63-0))
• 沸点：
  271.9±50.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  5-chloro-6-methyl-2-(methylthio)pyrimidin-4(3H)-one 在 palladium on activated charcoal 、 氢气 、 sodium hexamethyldisilazane 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基苯胺 为溶剂， 115.0 ℃ 、206.85 kPa 条件下， 反应 57.0h， 生成 2-(5-chloro-2-(methylthio)pyrimidin-4-yl)-1-(1-(trifluoromethyl)-cyclopropyl)ethenol
  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：

  6-甲基-4-羟基-2-甲硫基嘧啶 在 iron(III) chloride 、 磺酰氯 、 乙酸酐 、 溶剂黄146 作用下， 反应 36.0h， 以69%的产率得到5-chloro-6-methyl-2-(methylthio)pyrimidin-4(3H)-one
  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

文献信息

• Synthesis of Chloropyrimidines by Reaction with N-Chlorosuccinimide, and by Condensation Methods¹
  作者：Robert A. West、Harold W. Barrett

  DOI：10.1021/ja01641a009

  日期：1954.6
• GERSHON, H.;GREFIG, A. T., J. HETEROCYCL. CHEM., 1984, 21, N 4, 1161-1167
  作者：GERSHON, H.、GREFIG, A. T.

  DOI：——

  日期：——