N-(2,3,4,5,6-pentamethylbenzyl)imidazole | 1255762-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(2,3,4,5,6-pentamethylbenzyl)imidazole
• 英文别名: 1-pentamethylphenylmethyl-1H-imidazole；1-[(2,3,4,5,6-pentamethylphenyl)methyl]imidazole
• CAS: 1255762-71-0
• 化学式: C₁₅H₂₀N₂
• 分子量: 228.337
• InChiKey: JMPKHUBEEDGVQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-氯苯并噻唑 、 N-(2,3,4,5,6-pentamethylbenzyl)imidazole 在 ammonium hexafluorophosphate 作用下， 以 乙腈 、 水 为溶剂， 以76%的产率得到
  参考文献：
  名称：

  Novel NHC-coordinated ruthenium(II) arene complexes achieve synergistic efficacy as safe and effective anticancer therapeutics

  摘要：

  There is an urgent need for more effective, less toxic cancer therapy agents. Motivated by this need, we synthesized a small panel of N-heterocyclic carbene (NHC)-coordinated ruthenium(II) arene complexes Rul-Ru6 with the formula [Ru(p-cymene)(L)CIIPF6 (L = NHC ligand with varying substituents). Cell-based in vitro studies revealed that despite the structural similarity, Ru1-Ru6 exhibited distinct cytotoxic activities against cancer cells. In particular, Ru4 and Ru6, which bear n-octyl and pentamethylbenzyl motifs, respectively, were the most active at inducing apoptosis. In human ovarian A2780 cancer cells, Ru4 and Ru6 showed the highest cytotoxicities with IC50 values of 2.74 +/- 0.15 mu M and 1.98 +/- 0.10 mu M, respectively, and they were approximately 2-fold more potent than cisplatin (IC50 = 5.55 +/- 0.37 mu M). In addition to the cell killing capacity, inhibition of cell migration was validated by using these two optimized complexes. Mechanistic studies revealed that Ru4 and Ru6 complexes induced apoptosis in a caspase-dependent manner, primarily through intracellular reactive oxygen species (ROS) overproduction and cell cycle arrest at G1 phase. Furthermore, in a preclinical metastatic model of A2780 tumor xenograft, administration of Ru4 and Ru6 (20 mu mol/kg) resulted in a marked inhibition of tumor progression and metastasis. Finally, a substantially alleviated systemic toxicity was observed for both complexes in comparison with cisplatin in animals. Overall, this study greatly increases our understanding of NHC-coordinated Ru(II) arene metallodrugs, aiding further investigation of their therapeutic potential in the treatment of metastatic cancers. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112605
• 作为产物：
  描述：

  咪唑 、 2,3,4,5,6-五甲基苄氯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以87%的产率得到N-(2,3,4,5,6-pentamethylbenzyl)imidazole
  参考文献：
  名称：

  用于治疗皮质醇依赖性疾病的第一种选择性CYP11B1抑制剂。

  摘要：

  从基于依托咪酯的设计概念出发，我们成功开发了一系列高活性和选择性抑制剂CYP11B1（皮质醇生物合成的关键酶），作为治疗库欣综合症和相关疾病的潜在药物。因此，化合物33（IC50 = 152 nM）是第一种CYP11B1抑制剂，对最重要的类固醇生成CYP酶醛固酮合酶（CYP11B2），形成雄激素的CYP17和芳香​​酶（雌激素合酶CYP19）表现出相当好的选择性。

  DOI：

  10.1021/ml100071j

文献信息

• CN115850345
  申请人：——

  公开号：——

  公开（公告）日：——
• First Selective CYP11B1 Inhibitors for the Treatment of Cortisol-Dependent Diseases
  作者：Ulrike E. Hille、Christina Zimmer、Carsten A. Vock、Rolf W. Hartmann

  DOI：10.1021/ml100071j

  日期：2011.1.13

  concept, we succeeded in the development of a series of highly active and selective inhibitors of CYP11B1, the key enzyme of cortisol biosynthesis, as potential drugs for the treatment of Cushing's syndrome and related diseases. Thus, compound 33 (IC50 = 152 nM) is the first CYP11B1 inhibitor showing a rather good selectivity toward the most important steroidogenic CYP enzymes aldosterone synthase (CYP11B2)

  从基于依托咪酯的设计概念出发，我们成功开发了一系列高活性和选择性抑制剂CYP11B1（皮质醇生物合成的关键酶），作为治疗库欣综合症和相关疾病的潜在药物。因此，化合物33（IC50 = 152 nM）是第一种CYP11B1抑制剂，对最重要的类固醇生成CYP酶醛固酮合酶（CYP11B2），形成雄激素的CYP17和芳香​​酶（雌激素合酶CYP19）表现出相当好的选择性。
• Novel NHC-coordinated ruthenium(II) arene complexes achieve synergistic efficacy as safe and effective anticancer therapeutics
  作者：Chao Chen、Chang Xu、Tongyu Li、Siming Lu、Fangzhou Luo、Hangxiang Wang

  DOI：10.1016/j.ejmech.2020.112605

  日期：2020.10

  There is an urgent need for more effective, less toxic cancer therapy agents. Motivated by this need, we synthesized a small panel of N-heterocyclic carbene (NHC)-coordinated ruthenium(II) arene complexes Rul-Ru6 with the formula [Ru(p-cymene)(L)CIIPF6 (L = NHC ligand with varying substituents). Cell-based in vitro studies revealed that despite the structural similarity, Ru1-Ru6 exhibited distinct cytotoxic activities against cancer cells. In particular, Ru4 and Ru6, which bear n-octyl and pentamethylbenzyl motifs, respectively, were the most active at inducing apoptosis. In human ovarian A2780 cancer cells, Ru4 and Ru6 showed the highest cytotoxicities with IC50 values of 2.74 +/- 0.15 mu M and 1.98 +/- 0.10 mu M, respectively, and they were approximately 2-fold more potent than cisplatin (IC50 = 5.55 +/- 0.37 mu M). In addition to the cell killing capacity, inhibition of cell migration was validated by using these two optimized complexes. Mechanistic studies revealed that Ru4 and Ru6 complexes induced apoptosis in a caspase-dependent manner, primarily through intracellular reactive oxygen species (ROS) overproduction and cell cycle arrest at G1 phase. Furthermore, in a preclinical metastatic model of A2780 tumor xenograft, administration of Ru4 and Ru6 (20 mu mol/kg) resulted in a marked inhibition of tumor progression and metastasis. Finally, a substantially alleviated systemic toxicity was observed for both complexes in comparison with cisplatin in animals. Overall, this study greatly increases our understanding of NHC-coordinated Ru(II) arene metallodrugs, aiding further investigation of their therapeutic potential in the treatment of metastatic cancers. (C) 2020 Elsevier Masson SAS. All rights reserved.