2-[1-(3,5-diisopropyl-1H-pyrazol-1-yl)-2-(methylthio)ethyl]-4-methoxy-(3,5-dimethyl)pyridine | 1191928-11-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[1-(3,5-diisopropyl-1H-pyrazol-1-yl)-2-(methylthio)ethyl]-4-methoxy-(3,5-dimethyl)pyridine
• 英文别名: 2-(1-(3,5-diisopropyl-1H-pyrazol-1-yl)-3-(methylthio)ethyl)-4-methoxy-3,5-dimethylpyridine；CH3O(CH3)2C5HNCH(CH2SMe)C3HN2(iPr)2；2-[1-[3,5-Di(propan-2-yl)pyrazol-1-yl]-2-methylsulfanylethyl]-4-methoxy-3,5-dimethylpyridine；2-[1-[3,5-di(propan-2-yl)pyrazol-1-yl]-2-methylsulfanylethyl]-4-methoxy-3,5-dimethylpyridine
• CAS: 1191928-11-6
• 化学式: C₂₀H₃₁N₃OS
• 分子量: 361.552
• InChiKey: YJSFDTFGGWYDIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tetrakis(acetonitrile)copper(I)tetrafluoroborate 、 2-[1-(3,5-diisopropyl-1H-pyrazol-1-yl)-2-(methylthio)ethyl]-4-methoxy-(3,5-dimethyl)pyridine 以 丙酮 为溶剂， 以94%的产率得到[bis(acetonitrile)bis(2-(1-(3,5-diisopropyl-1H-pyrazol-1-yl)-3-(methylthio)ethyl)-4-methoxy-3,5-dimethylpyridine)dicopper(I)] tetrafluoroborate
  参考文献：
  名称：

  新型以碳为中心的异蝎子配体：Cu（I）配合物和发光性能

  摘要：

  摘要本文描述了N，N'，S供体配体2-（1-（3,5-二异丙基-1H-吡唑-1-基）-3-（甲硫基）丙基）-4-甲氧基-3的合成1，5-二甲基吡啶（L1）和2-（1-（3，5-二异丙基-1H-吡唑-1-基）-2-（甲硫基）乙基）-4-甲氧基-3，5-二甲基吡啶（L2）。通过使L1或L2与[Cu（CH3CN）4] BF4或CuCl反应制备Cu（I）配合物。发现配体的硫醚臂的配位行为决定了所得配合物的核，其中[Cu（L1）PPh3] BF4（1）为多核，[Cu（L2）PPh3] BF4（2）为单核，而[Cu（L1）] 2（BF4）2（3），[Cu（L2）CH3CN] 2（BF4）2（4）和[Cu（L1）Cl] 2（5）是双核的。在二聚体[Cu（L2）Cl] 2（6）中，硫原子没有金属结合。而是，两个桥接氯离子连接两个铜中心。化合物4–6以固态发光，并显示分别位于490 nm（4），544 nm（5）和562

  DOI：

  10.1016/j.ica.2009.05.014
• 作为产物：
  描述：

  氯甲基甲硫醚 、 2-[(3,5-diisopropyl-1H-pyrazol-1-yl)methyl]-4-methoxy-3,5-dimethylpyridine 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以55%的产率得到2-[1-(3,5-diisopropyl-1H-pyrazol-1-yl)-2-(methylthio)ethyl]-4-methoxy-(3,5-dimethyl)pyridine
  参考文献：
  名称：

  Copper Binding Agents Acting as Copper Ionophores Lead to Caspase Inhibition and Paraptotic Cell Death in Human Cancer Cells

  摘要：

  We report a quantitative structure activity relationship study of a new class of pyrazole-pyridine copper complexes that establishes a clear correlation between the ability to promote copper accumulation and cytotoxicity. Intracellular metal accumulation is maximized when ligand lipophilicity allows the complex to rapidly cross the membrane. Copper and ligand follow different uptake kinetics and reach different intracellular equilibrium concentrations. These results support a model in which the ligand acts as an ionophore for the metal ion, cycling between intra- and extracellular compartments as dissociated or complexed entities. When treating cancer cells with structurally unrelated disulfiram and pyrazole-pyridine copper complexes, as well as with inorganic copper, the same morphological and molecular changes were reproduced, indicating that copper overload is responsible for the cytotoxic effects. Copper-based treatments drive sensitive cancer cells toward paraptotic cell death, a process hallmarked by endoplasmic reticulum stress and massive vacuolization in the absence of apoptotic features. A lack of caspase activation, as observed in copper-treated dying cells, is a consequence of metal-mediated inhibition of caspase-3. Thus, copper acts simultaneously as an endoplasmic reticulum (ER) stress inducer and a caspase-3 inhibitor, forcing the cell into caspase-independent paraptotic death. The establishment of a mechanism of action common to different copper binding agents provides a rationale for the exploitation of copper toxicity as an anticancer tool.

  DOI：

  10.1021/ja109413c