2-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-4-methoxy-3,5-dimethylpyridine | 1292840-64-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-4-methoxy-3,5-dimethylpyridine
• 英文别名: CH3O(CH3)2C5HNCH2C3HN2(Me)2；2-[(3,5-Dimethylpyrazol-1-yl)methyl]-4-methoxy-3,5-dimethylpyridine
• CAS: 1292840-64-2
• 化学式: C₁₄H₁₉N₃O
• mdl: MFCD19011407
• 分子量: 245.324
• InChiKey: YMASZZDXLXMQTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  氯甲基甲硫醚 、 2-[(3,5-dimethyl-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41%的产率得到2-[1-(3,5-dimethyl-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
• 作为产物：
  描述：

  3,5-二甲基吡唑 、 2-氯甲基-3,5-二甲基-4-甲氧基吡啶盐酸盐 在 四丁基氢氧化铵 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 4.0h， 以85%的产率得到2-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-4-methoxy-3,5-dimethylpyridine
  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

文献信息

• Synthesis and Characterization of Silver(I) Pyrazolylmethylpyridine Complexes and Their Implementation as Metallic Silver Thin Film Precursors
  作者：Irene Bassanetti、Christina P. Twist、Myung-Gil Kim、Afif M. Seyam、Hassan S. Bazzi、Q. Jane Wang、Yip-Wah Chung、Luciano Marchió、Massimiliano Delferro、Tobin J. Marks

  DOI：10.1021/ic500321w

  日期：2014.5.5

  A series of light- and air-stable silver(I) pyrazolylmethylpyridine complexes [Ag(L-R)](n)(BF4)(n) (L = pyrazolylmethylpyridine; R = H, 1; R = Me, 2; R = i-Pr, 3) and [Ag(L-R)(NO3)](2) (L = pyrazolylmethylpyridine; R = H, 4; R = Me, 5; R = i-Pr, 6) has been synthesized and structurally and spectroscopically characterized. In all of the molecular structures, the pyrazolylmethylpyridine ligands bridge two metal centers, thus giving rise to dinuclear (2, 4, 5, and 6) or polynuclear structures (1 and 3). The role played by the counteranions is also of relevance, because dimeric structures are invariably obtained with NO3- (4, 5, and 6), whereas the less-coordinating BF4- counteranion affords polymeric structures (1 and 3). Also, through atoms-in-molecules (AIM) analysis of the electron density, an argentophilic Ag...Ag interaction is found in complexes 2 and 4. Thermogravimetric analysis (TGA) shows that the thermolytic properties of the present complexes can be significantly modified by altering the ligand structure and counteranion. These complexes were further investigated as thin silver film precursors by spin-coating solutions, followed by annealing at 310 degrees C on 52100 steel substrates. The resulting polycrystalline cubic-phase Ag films of similar to 55 nm thickness exhibit low levels of extraneous element contamination by X-ray photoelectron spectroscopy (XPS). Atomic force microscopy (AFM) and scanning electron microscopy (SEM) indicate that film growth proceeds primarily via an island growth (Volmer-Weber) mechanism. Complex 4 was also evaluated as a lubricant additive in ball-on-disk tribological tests. The results of the friction evaluation and wear measurements indicate a significant reduction in wear (similar to 88%) at optimized Ag complex concentrations with little change in friction. The enhanced wear performance is attributed to facile shearing of Ag metal in the contact region, resulting from thermolysis of the silver complexes, and is confirmed by energy-dispersive X-ray analysis of the resulting wear scars.
• Copper Binding Agents Acting as Copper Ionophores Lead to Caspase Inhibition and Paraptotic Cell Death in Human Cancer Cells
  作者：Saverio Tardito、Irene Bassanetti、Chiara Bignardi、Lisa Elviri、Matteo Tegoni、Claudio Mucchino、Ovidio Bussolati、Renata Franchi-Gazzola、Luciano Marchiò

  DOI：10.1021/ja109413c

  日期：2011.4.27

  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.