4,6-dichloro-2-(m-tolylthio)pyrimidine | 1394124-21-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4,6-dichloro-2-(m-tolylthio)pyrimidine
• 英文别名: 4,6-Dichloro-2-(3-methylphenyl)sulfanylpyrimidine
• CAS: 1394124-21-0
• 化学式: C₁₁H₈Cl₂N₂S
• 分子量: 271.17
• InChiKey: OPFYCFNHAYLYRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.24
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  25.78
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-2-(m-tolylthio)pyrimidine 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(5-methyl-1H-pyrazol-3-yl)-2-[(3-methylphenyl)sulfanyl]-6-(4-methylpiperazin-1-yl)pyrimidin-4-amine
  参考文献：
  名称：

  From Cancer to Pain Target by Automated Selectivity Inversion of a Clinical Candidate

  摘要：

  Elimination of inadvertent binding is crucial for inhibitor design targeting conserved protein classes like kinases. Compounds in clinical trials provide a rich source for initiating drug design efforts by exploiting such secondary binding events. Considering both aspects, we shifted the selectivity of tozasertib, originally developed against AurA as cancer target, toward the pain target TrkA. First, selectivity-determining features in binding pockets were identified by fusing interaction grids of several key and off-target conformations. A focused library was subsequently created and prioritized using a multiobjective selection scheme that filters for selective and highly active compounds based on orthogonal methods grounded in computational chemistry and machine learning. Eighteen high-ranking compounds were synthesized and experimentally tested. The top-ranked compound has 10000-fold improved selectivity versus AurA, nanomolar cellular activity, and is highly selective in a kinase panel. This was achieved in a single round of automated in silico optimization, highlighting the power of recent advances in computer-aided drug design to automate design and selection processes.

  DOI：

  10.1021/acs.jmedchem.8b00140
• 作为产物：
  描述：

  3-甲基苯硫酚 、 4,6-二氯-2-甲砜基嘧啶 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 1.5h， 以62%的产率得到4,6-dichloro-2-(m-tolylthio)pyrimidine
  参考文献：
  名称：

  新型基于β-甲氧基丙烯酸酯的Strobilurin类似物的合成及抗真菌活性

  摘要：

  嗜球果伞素已成为最重要的农业杀真菌剂之一。为了发现对耐药病原体具有高活性的新球果伞素衍生物，通过将取代的嘧啶与球果伞素药效团整合在一起，设计并合成了一系列新型的β-甲氧基丙烯酸酯类似物。通过红外，1 H核磁共振，元素分析和质谱对化合物进行了确认和表征。生物测定表明，大多数化合物1对球形炭疽菌，灰葡萄孢菌和辣椒疫霉均表现出有效的抗真菌活性。浓度为50μg/ mL的Leonian。令人振奋的是，化合物1a（R =甲基）对所有测试真菌的抗真菌活性均优于市售的伞形姜黄素杀真菌剂嘧菌酯。

  DOI：

  10.1002/cjoc.201200101