2,6-bis((1H-imidazol-1-yl)methyl)-4-methylphenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2,6-bis((1H-imidazol-1-yl)methyl)-4-methylphenol
• 英文别名: 2,6-bis(imidazol-1-yl)methyl-4-methylphenol；2,6-Bis(imidazol-1-ylmethyl)-4-methylphenol
• 化学式: C₁₅H₁₆N₄O
• 分子量: 268.318
• InChiKey: ILPBGYPAVICUNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-5,6-dimethylpyridine-3,4-dicarbonitrile 、 2,6-bis((1H-imidazol-1-yl)methyl)-4-methylphenol 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 18.25h， 以73%的产率得到2-{2,6-bis[(1H-imidazol-1-yl)methyl]-4-methylphenoxy}-5,6-dimethylpyridine-3,4-dicarbonitrile
  参考文献：
  名称：

  Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers

  摘要：

  Investigation of a series of tetra(3,4-pyrido)porphyrazines (TPyPzs) substituted with hydrophilic substituents revealed important structure activity relationships for their use in photodynamic therapy (PDT). Among them, a cationic TPyPz derivative with total of 12 cationic charges above, below and in the plane of the core featured a unique spatial arrangement that caught the hydrophobic core in a cage, thereby protecting it fully from aggregation in water. This derivative exhibited exceptionally effective photodynamic activity on a number of tumor cell lines (HeLa, SK-MEL-28, A549, MCF-7) with effective concentrations (EC50) typically below 5 nM, at least an order of magnitude better than the EC50 values obtained for the clinically approved photosensitizers verteporfin, temoporfin, protoporphyrin IX, and trisulfonated hydroxyaluminum phthalocyanine. Its very low dark toxicity (TC50 > 400 mu M) and high ability to induce photo damage to endothelial cells (EA.hy926) without preincubation suggest the high potential of this cationic TPyPz derivative in vascular-targeted PDT.

  DOI：

  10.1021/acs.jmedchem.6b01140
• 作为产物：
  描述：

  咪唑 、 4-叔-丁基-2,6-二(羟基甲基)苯酚 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以42.7%的产率得到2,6-bis((1H-imidazol-1-yl)methyl)-4-methylphenol
  参考文献：
  名称：

  Self-assembly from metal–organic vesicles to globular networks: metallogel-mediated phenylation of indole with phenyl boronic acid

  摘要：

  描述了构象灵活的双甲基咪唑配体与Pd(OAc)2的自组装。根据配体是否提供氢键供体，实现了金属有机囊泡向球状网络凝胶溶剂的转变。这些金属凝胶在吲哚与苯硼酸的交叉耦合反应中表现出催化活性。

  DOI：

  10.1039/c0cc00112k

文献信息

• Water-soluble non-aggregating zinc phthalocyanine and in vitro studies for photodynamic therapy
  作者：Saad Makhseed、Miloslav Machacek、Waleed Alfadly、Ahmad Tuhl、Mickey Vinodh、Tomas Simunek、Veronika Novakova、Pavel Kubat、Emil Rudolf、Petr Zimcik

  DOI：10.1039/c3cc44609c

  日期：——

  Newly synthesized zinc phthalocyanine bearing sixteen quaternized imidazolyl moieties on the periphery displays high water-solubility, lack of aggregation and high singlet oxygen quantum yield in water (ΦΔ > 0.33). The in vitro tests indicated excellent anticancer photodynamic activity (EC50 = 36.7 nM) and low dark toxicity to non-cancerous cells (TC50 = 395 μM).

  新合成的酞菁锌外围含有十六个季铵化咪唑基，在水中具有高水溶性、无聚集性和高单线态氧量子产率（ΦΔ > 0.33）。体外测试表明，它具有出色的抗癌光动力活性（EC50 = 36.7 nM），对非癌细胞的暗毒性较低（TC50 = 395 μM）。
• Direct Imidazolylmethylation of Phenols
  作者：Jia-Ming Yan、Zhu-Jun Zhang、De-Qi Yuan、Ru-Gang Xie、Hua-Ming Zhao

  DOI：10.1080/00397919408012624

  日期：1994.1

  Abstract Direct imidazolylmethylation of phenols was realized by Mannich reaction of phenols with paraformaldehyde and imidazole.

  摘要 通过苯酚与多聚甲醛和咪唑的曼尼希反应实现苯酚的直接咪唑基甲基化。
• New Highly Fluorescent Water Soluble Imidazolium-Perylenediimides: Synthesis and Cellular Response
  作者：José Garcés-Garcés、Miguel Sánchez-Martos、Gema Martinez-Navarrete、Eduardo Fernández-Jover、Mirela Encheva、Martín León、Javier Ortiz、Ángela Sastre-Santos、Fernando Fernández-Lázaro

  DOI：10.3390/pharmaceutics15071892

  日期：——

  the specific locations of both PDIs within the lysosomes and mitochondria. In vitro studies were conducted to evaluate the anticancer activity of PDI-1 and PDI-2. Remarkably, these photosensitizers demonstrated a significant ability to selectively eliminate cancer cells when exposed to a specific light wavelength. The water solubility, high fluorescence quantum yield, and selective cytotoxicity of these

  描述了两种新型水溶性2,6-双(咪唑基甲基)-4-甲基苯氧基含苝二酰亚胺PDI-1和PDI-2的合成和表征。这些化合物在水中表现出高荧光量子产率，并被研究作为潜在的光敏剂，用于产生活性氧并应用于抗癌活性。HeLa 细胞系 (VPH18) 用于评估其功效。采用荧光显微镜确认 PDI-1 和 PDI-2 的成功内化，而共聚焦显微镜则揭示了两种 PDI 在溶酶体和线粒体内的具体位置。进行体外研究以评估 PDI-1 和 PDI-2 的抗癌活性。值得注意的是，这些光敏剂在暴露于特定的光波长时表现出选择性消除癌细胞的显着能力。这些 PDI 的水溶性、高荧光量子产率和对癌细胞的选择性细胞毒性凸显了它们作为靶向光动力治疗有效药物的潜力。总之，本文提出的研究结果为未来探索和优化 PDI-1 和 PDI-2 作为光动力疗法中有效的光敏剂奠定了坚实的基础，可能会改善癌症患者的治疗策略。
• Self-assembly from metal–organic vesicles to globular networks: metallogel-mediated phenylation of indole with phenyl boronic acid
  作者：Li Yang、Liang Luo、Shuai Zhang、Xiaoyu Su、Jingbo Lan、Chi-Tien Chen、Jingsong You

  DOI：10.1039/c0cc00112k

  日期：——

  Self-assembly of the conformationally flexible bismethylimidazolyl ligands with Pd(OAc)2 is described. Depending on whether the ligands provide the hydrogen bonding donor, a switching of metal–organic vesicles to globular networks gelating solvents is achieved. The metallogels exhibit catalytic activity for the cross-coupling of indole with phenyl boronic acid.

  描述了构象灵活的双甲基咪唑配体与Pd(OAc)2的自组装。根据配体是否提供氢键供体，实现了金属有机囊泡向球状网络凝胶溶剂的转变。这些金属凝胶在吲哚与苯硼酸的交叉耦合反应中表现出催化活性。
• Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers
  作者：Miloslav Machacek、Jiri Demuth、Pavel Cermak、Magda Vavreckova、Lenka Hruba、Adela Jedlickova、Pavel Kubat、Tomas Simunek、Veronika Novakova、Petr Zimcik

  DOI：10.1021/acs.jmedchem.6b01140

  日期：2016.10.27

  Investigation of a series of tetra(3,4-pyrido)porphyrazines (TPyPzs) substituted with hydrophilic substituents revealed important structure activity relationships for their use in photodynamic therapy (PDT). Among them, a cationic TPyPz derivative with total of 12 cationic charges above, below and in the plane of the core featured a unique spatial arrangement that caught the hydrophobic core in a cage, thereby protecting it fully from aggregation in water. This derivative exhibited exceptionally effective photodynamic activity on a number of tumor cell lines (HeLa, SK-MEL-28, A549, MCF-7) with effective concentrations (EC50) typically below 5 nM, at least an order of magnitude better than the EC50 values obtained for the clinically approved photosensitizers verteporfin, temoporfin, protoporphyrin IX, and trisulfonated hydroxyaluminum phthalocyanine. Its very low dark toxicity (TC50 > 400 mu M) and high ability to induce photo damage to endothelial cells (EA.hy926) without preincubation suggest the high potential of this cationic TPyPz derivative in vascular-targeted PDT.