2-(methylthio)-4-((trimethylsilyl)ethynyl)pyrimidine | 544675-63-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(methylthio)-4-((trimethylsilyl)ethynyl)pyrimidine
• 英文别名: 2-Methylsulfanyl-4-trimethylsilanylethynyl-pyrimidine；2-(Methylsulfanyl)-4-[(trimethylsilyl)ethynyl]pyrimidine；trimethyl-[2-(2-methylsulfanylpyrimidin-4-yl)ethynyl]silane
• CAS: 544675-63-0
• 化学式: C₁₀H₁₄N₂SSi
• 分子量: 222.386
• InChiKey: AEHZGEDBUHMEKM-UHFFFAOYSA-N

物化性质

• 沸点：
  293.1±22.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.43
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 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：

  2-(methylthio)-4-((trimethylsilyl)ethynyl)pyrimidine 在 甲醇 、 potassium fluoride 、 氢氧化钾 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 21.17h， 生成 3-(2-methylsulfonylpyrimidin-4-yl)pyrazolo[1,5-b]pyridazine
  参考文献：
  名称：

  N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as Potent and Selective Inhibitors of Glycogen Synthase Kinase 3 with Good Cellular Efficacy

  摘要：

  Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm040063i
• 作为产物：
  描述：

  2-甲硫基-4-氯嘧啶 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 氢碘酸 、 三乙胺 作用下， 反应 28.0h， 生成 2-(methylthio)-4-((trimethylsilyl)ethynyl)pyrimidine
  参考文献：
  名称：

  N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as Potent and Selective Inhibitors of Glycogen Synthase Kinase 3 with Good Cellular Efficacy

  摘要：

  Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm040063i

文献信息

• Structure-Activity Relationships of 2-Sufonylpyrimidines as Quorum-Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of<i>Pseudomonas aeruginosa</i>
  作者：Andreas Thomann、Christian Brengel、Carsten Börger、Dagmar Kail、Anke Steinbach、Martin Empting、Rolf W. Hartmann

  DOI：10.1002/cmdc.201600419

  日期：2016.11.21

  Herein we report the structure–activity relationships of 2‐sulfonylpyrimidines, which were previously identified as dual‐target inhibitors of the PQS receptor PqsR and the PQS synthase PqsD. The SAR elucidation was guided by a combined approach using ligand efficiency and ligand lipophilicity efficiency to select the most promising compounds. In addition, the most effective inhibitors were rationally modified

  耐药的铜绿假单胞菌（PA）菌株正在增加，使目前的抗生素治疗无效。因此，迫切需要通过新方法来克服耐药性或恢复抗生素的活性。针对假单胞菌喹诺酮信号定点感应（PQS-QS）系统是一种在不影响PA致病性的情况下消除PA致病性的有趣策略。在这里，我们报告2-磺酰基嘧啶的结构-活性关系，后者先前被确定为PQS受体PqsR和PQS合酶PqsD的双靶标抑制剂。SAR的阐明是通过使用配体效率和配体亲脂性效率的组合方法来选择最有前途的化合物。此外，使用Hansch分析在QSAR的指导下合理地修饰了最有效的抑制剂。最后，这些抑制剂显示出减少生物膜质量和细胞外DNA的能力，这是决定抗生素耐药性的重要因素。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSES CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005016914A1

  公开（公告）日：2005-02-24

  The present invention discloses pyrimidine derivatives, compositions and medicaments containing the same, as well as processes for the preparation and use of such compounds, compositions and medicaments. Such pyrimidine derivatives are useful in the treatment of diseases associated with inappropriate ErbB family kinase.

  本发明公开了嘧啶衍生物，含有该嘧啶衍生物的组合物和药物，以及制备和使用这些化合物、组合物和药物的方法。这些嘧啶衍生物在治疗与不适当的ErbB家族激酶相关的疾病中很有用。
• [EN] PYRADAZINE COMPOUNDS AS GSK-3 INHIBITORS<br/>[FR] COMPOSES DE PYRADAZINE UTILES COMME INHIBITEURS DE GSK-3
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004035588A1

  公开（公告）日：2004-04-29

  The present invention relates generally to inhibitors of the kinases, such as GSK3, and more particularly to fused pyradazine compounds according to formula (I) and methods of their use.

  本发明通常涉及激酶抑制剂，如GSK3，更具体地涉及根据式(I)的融合吡啶并嘧啶化合物及其使用方法。
• Pyrazolo-pyridine derivatives as antiherpes agents
  申请人：——

  公开号：US20040248903A1

  公开（公告）日：2004-12-09

  The present invention provides compounds of formula (I): 1 wherein all variables are as defined herein, pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

  本发明提供了式(I)的化合物：1其中所有变量如本文所定义，包含它们的药物组合物，制备它们的过程以及它们作为药物制剂的用途。
• Pyrazolo-Pyridine Derivatives As Antiherpes Agents
  申请人：Gudmundsson Kristjan

  公开号：US20070161653A1

  公开（公告）日：2007-07-12

  The present invention provides compounds of formula (I): wherein all variables are as defined herein, pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

  本发明提供公式(I)的化合物：其中所有变量均如此定义，包含该化合物的药物组合物，制备该化合物的过程以及它们作为药物制剂的用途。