21-methyl-8,17-dioxa-19,21-diazatricyclo[16.2.1.02,7]henicosa-1(20),2,4,6,13,18-hexaene | 1236073-87-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 21-methyl-8,17-dioxa-19,21-diazatricyclo[16.2.1.02,7]henicosa-1(20),2,4,6,13,18-hexaene
• CAS: 1236073-87-2
• 化学式: C₁₈H₂₂N₂O₂
• 分子量: 298.385
• InChiKey: AGLKQNJMUAORON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  22.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  36.28
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  21-methyl-8,17-dioxa-19,21-diazatricyclo[16.2.1.02,7]henicosa-1(20),2,4,6,13,18-hexaene 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 21-methyl-8,17-dioxa-19,21-diazatricyclo[16.2.1.0(2,7)]henicosa-1(20),2,4,6,18-pentaene
  参考文献：
  名称：

  含咪唑大环化合物的平面手性 - 理解和调整阻转异构

  摘要：

  已经实现了显示平面手性的含咪唑大环的合成和表征。HLPC 和 NMR 研究揭示了脂环链长度在决定立体异构化速率方面的关键作用：15 和 16 元环状化合物是手性的，而它们的大环类似物在室温下迅速平衡。计算计算与实验观察结果非常一致，使我们能够了解两种阻转异构体之间的构象平衡所涉及的机制和相互作用。通过半制备手性 HPLC 分离 15 元大环的两种对映异构体使我们能够研究手性对其生物活性的影响。

  DOI：

  10.1002/ejoc.201100805
• 作为产物：
  描述：

  5-hexenyl methanesulfonate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 四(三苯基膦)钯 、 正丁基锂 、 四丁基碘化铵 、 sodium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 21-methyl-8,17-dioxa-19,21-diazatricyclo[16.2.1.02,7]henicosa-1(20),2,4,6,13,18-hexaene
  参考文献：
  名称：

  New 5-Aryl-1H-imidazoles Display in Vitro Antitumor Activity against Apoptosis-Resistant Cancer Models, Including Melanomas, through Mitochondrial Targeting

  摘要：

  We designed and synthesized 48 aryl-1H-imidazole derivatives and investigated their in vitro growth inhibitory activity in cancer cell lines known to present various levels of resistance to proapoptotic stimuli. The IC50 in vitro growth inhibitory concentration of these compounds ranged from >100 mu M to single digit mu M. Among the most active compounds, 2i displayed similar in vitro growth inhibition in cancer cells independent of the cells' levels of resistance to proapoptotic stimuli and was found to be cytostatic in melanoma cell lines. Compound 2i was then tested by the National Cancer Institute Human Tumor Cell Line Anti-Cancer Drug Screen, and the NCI COMPARE algorithm did not reveal any correlation between its growth inhibition profiles with the NCI database compound profiles. The use of transcriptomically characterized melanoma models then enabled us to highlight mitochondrial targeting by 2i. This hypothesis was further confirmed by reactive oxygen production measurement and oxygen consumption analysis.

  DOI：

  10.1021/jm400287v

文献信息

• Planar Chirality of Imidazole-Containing Macrocycles - Understanding and Tuning Atropisomerism
  作者：Emilie Van Den Berge、Jiří Pospíšil、Tran Trieu-Van、Laurent Collard、Raphaël Robiette

  DOI：10.1002/ejoc.201100805

  日期：2011.11

  The synthesis and characterization of imidazole-containing macrocycles displaying planar chirality has been achieved. HLPC and NMR studies revealed the crucial role of the alicyclic chain length in determining the rate of stereoisomerisation: 15- and 16-membered cyclic compounds are chiral whereas their larger-ringed analogues equilibrate rapidly at room temperature. Computational calculations are

  已经实现了显示平面手性的含咪唑大环的合成和表征。HLPC 和 NMR 研究揭示了脂环链长度在决定立体异构化速率方面的关键作用：15 和 16 元环状化合物是手性的，而它们的大环类似物在室温下迅速平衡。计算计算与实验观察结果非常一致，使我们能够了解两种阻转异构体之间的构象平衡所涉及的机制和相互作用。通过半制备手性 HPLC 分离 15 元大环的两种对映异构体使我们能够研究手性对其生物活性的影响。
• New 5-Aryl-1<i>H</i>-imidazoles Display in Vitro Antitumor Activity against Apoptosis-Resistant Cancer Models, Including Melanomas, through Mitochondrial Targeting
  作者：Véronique Mathieu、Emilie Van Den Berge、Justine Ceusters、Tomasz Konopka、Antonin Cops、Céline Bruyère、Christine Pirker、Walter Berger、Tran Trieu-Van、Didier Serteyn、Robert Kiss、Raphaël Robiette

  DOI：10.1021/jm400287v

  日期：2013.9.12

  We designed and synthesized 48 aryl-1H-imidazole derivatives and investigated their in vitro growth inhibitory activity in cancer cell lines known to present various levels of resistance to proapoptotic stimuli. The IC50 in vitro growth inhibitory concentration of these compounds ranged from >100 mu M to single digit mu M. Among the most active compounds, 2i displayed similar in vitro growth inhibition in cancer cells independent of the cells' levels of resistance to proapoptotic stimuli and was found to be cytostatic in melanoma cell lines. Compound 2i was then tested by the National Cancer Institute Human Tumor Cell Line Anti-Cancer Drug Screen, and the NCI COMPARE algorithm did not reveal any correlation between its growth inhibition profiles with the NCI database compound profiles. The use of transcriptomically characterized melanoma models then enabled us to highlight mitochondrial targeting by 2i. This hypothesis was further confirmed by reactive oxygen production measurement and oxygen consumption analysis.