4,5-Dichloro-6-methyl-2-methylthiopyrimidine | 63331-69-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4,5-Dichloro-6-methyl-2-methylthiopyrimidine
• 英文别名: 4,5-Dichloro-6-methyl-2-(methylthio)pyrimidine；4,5-dichloro-6-methyl-2-methylsulfanylpyrimidine
• CAS: 63331-69-1
• 化学式: C₆H₆Cl₂N₂S
• 分子量: 209.099
• InChiKey: FMCVLHRVFLGMJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 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：
  51.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-Dichloro-6-methyl-2-methylthiopyrimidine 在 palladium on activated charcoal 、 氢气 、 sodium hydroxide 作用下， 以 水 为溶剂， 20.0 ℃ 、206.85 kPa 条件下， 反应 24.0h， 以75%的产率得到5-氯-4-甲基-2-(甲硫基)嘧啶
  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：

  5-Chloro-6-methyl-2-methylthiopyrimidin-4-ol 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 反应 3.0h， 以76%的产率得到4,5-Dichloro-6-methyl-2-methylthiopyrimidine
  参考文献：
  名称：

  Gershon, Herman; Grefig, Anthony T., Journal of Heterocyclic Chemistry, 1984, vol. 21, p. 1161 - 1167

  摘要：

  DOI：

文献信息

• 5-Halopyrimid-2-ones
  申请人：Nyegaard & Co. A/S

  公开号：US04395406A1

  公开（公告）日：1983-07-26

  Novel derivatives of pyrimid-2-one having interesting pharmacological properties are described. The compounds of the invention have been found to be of use in the control of, and in particular in the inhibition of the metaphase of malignant tumours and leukaemias. Processes for the preparation of the novel compounds and pharmaceutical compositions containing them are also described.

  描述了具有有趣药理特性的嘧啶-2-酮的新衍生物。本发明的化合物已被发现可用于控制和特别是抑制恶性肿瘤和白血病的中期有用。还描述了制备新化合物的方法和含有它们的药物组合物。
• GERSHON, H.;GREFIG, A. T., J. HETEROCYCL. CHEM., 1984, 21, N 4, 1161-1167
  作者：GERSHON, H.、GREFIG, A. T.

  DOI：——

  日期：——
• US4395406A
  申请人：——

  公开号：US4395406A

  公开（公告）日：1983-07-26
• Gershon, Herman; Grefig, Anthony T., Journal of Heterocyclic Chemistry, 1984, vol. 21, p. 1161 - 1167
  作者：Gershon, Herman、Grefig, Anthony T.

  DOI：——

  日期：——
• Lead Optimization toward Proof-of-Concept Tools for Huntington’s Disease within a 4-(1<i>H</i>-Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors
  作者：John Wityak、Kevin F. McGee、Michael P. Conlon、Ren Hua Song、Bryan C. Duffy、Brent Clayton、Michael Lynch、Gwen Wang、Emily Freeman、James Haber、Douglas B. Kitchen、David D. Manning、Jiffry Ismail、Yuri Khmelnitsky、Peter Michels、Jeff Webster、Macarena Irigoyen、Michele Luche、Monica Hultman、Mei Bai、IokTeng D. Kuok、Ryan Newell、Marieke Lamers、Philip Leonard、Dawn Yates、Kim Matthews、Lynette Ongeri、Steve Clifton、Tania Mead、Susan Deupree、Pat Wheelan、Kathy Lyons、Claire Wilson、Alex Kiselyov、Leticia Toledo-Sherman、Maria Beconi、Ignacio Muñoz-Sanjuan、Jonathan Bard、Celia Dominguez

  DOI：10.1021/jm5013598

  日期：2015.4.9

  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.