11-amino-12-(4-dimethylaminophenyl)-7,9,10,12-tetrahydro-8H-5-oxa-6-aza-naphthacen-3-ol | 1240216-76-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 11-amino-12-(4-dimethylaminophenyl)-7,9,10,12-tetrahydro-8H-5-oxa-6-aza-naphthacen-3-ol
• 英文别名: 11-amino-12-[4-(dimethylamino)phenyl]-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ol
• CAS: 1240216-76-5
• 化学式: C₂₄H₂₅N₃O₂
• 分子量: 387.481
• InChiKey: UPTDWPPEPOMIMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  71.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-amino-4-(4-dimethylaminophenyl)-7-hydroxy-4H-chromene-3-carbonitrile 、 环己酮 在 aluminum (III) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 0.13h， 以85%的产率得到11-amino-12-(4-dimethylaminophenyl)-7,9,10,12-tetrahydro-8H-5-oxa-6-aza-naphthacen-3-ol
  参考文献：
  名称：

  在受控微波辐射下快速合成涉及色烯的新型吡喃并吡啶衍生物

  摘要：

  2-氨基-3-氰基-4H-色烯和环己酮在氯化铝存在下，在受控的微波辐射下进行环缩合反应，实现了新型吡喃并[2,3-b]吡啶衍生物的有效合成。实验条件已经过彻底优化和建立，可以显着提高速率和优异的产量。使用一锅 DBU 催化的微波诱导间苯二酚、丙二腈和芳香醛的多组分缩合获得起始 4H-色烯。

  DOI：

  10.3998/ark.5550190.0011.a25

文献信息

• An expeditious synthesis of novel pyranopyridine derivatives involving chromenes under controlled microwave irradiation
  作者：Dushyant Singh Raghuvanshi、Krishna Nand Singh

  DOI：10.3998/ark.5550190.0011.a25

  日期：——

  An efficient synthesis of novel pyrano[2,3-b]pyridine derivatives has been achieved by the cyclocondensation of 2-amino-3-cyano-4H-chromenes and cyclohexanone in the presence of aluminium chloride under controlled microwave irradiation. The experimental conditions have been thoroughly optimized and established, allowing significant rate enhancements and excellent yields. The starting 4H-chromenes were

  2-氨基-3-氰基-4H-色烯和环己酮在氯化铝存在下，在受控的微波辐射下进行环缩合反应，实现了新型吡喃并[2,3-b]吡啶衍生物的有效合成。实验条件已经过彻底优化和建立，可以显着提高速率和优异的产量。使用一锅 DBU 催化的微波诱导间苯二酚、丙二腈和芳香醛的多组分缩合获得起始 4H-色烯。
• Toxicological and pharmacological evaluation, antioxidant, ADMET and molecular modeling of selected racemic chromenotacrines {11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ols} for the potential prevention and treatment of Alzheimer's disease
  作者：María Jesús Oset-Gasque、María Pilar González、Javier Pérez-Peña、Nuria García-Font、Alejandro Romero、Javier del Pino、Eva Ramos、Dimitra Hadjipavlou-Litina、Elena Soriano、Mourad Chioua、Abdelouahid Samadi、Dushyant S. Raghuvanshi、Krishna N. Singh、José Marco-Contelles

  DOI：10.1016/j.ejmech.2013.12.021

  日期：2014.3

  The pharmacological analysis of racemic chromenotacrines (CT) 1-7, bearing the 11-amino-12-aryl-8,9,10,12tetrahydro-7H-chromeno[2,3-b]quinolin-3-ol ring skeleton, in a series of experiments targeted to explore their potential use for the treatment of Alzheimer's disease (AD), is reported. The toxicological evaluation showed that among all these chromenotacrines, CT6 is much less hepatotoxic than tacrine in a range of concentrations from 1 to 300 mu M, measured as cell viability in HepG2 cells. Moreover, CT6 did not significantly increase lactate dehydrogenase, aspartate transaminase, and alanine transaminase release in HepG2 cells. Besides, CT6 treatment exerts a high protective effect against the lipid peroxidation induced after H2O2-treated SH-SY5Y cells, in a concentration-dependent manner. cm showed an excellent antioxidant profile in the AAPH test, and protects against the decrease in cell viability induced by respiratory chain inhibitors (Oligomicyn A/Rotenone) and NO donors in neuronal cultures. This effect could be due to a mixed antiapoptotic and antinecrotic neuroprotective effect at low and intermediate CT6 concentrations, respectively. CT1-7 are potent and selective inhibitors of EeAChE in the submicromolar range. CT3 [IC50 (EeAChE) = 0.007 +/- 0.003 mu M], and CT6 IC50 (EeAChE) = 0.041 +/- 0.001 mu M are the most potent AChE inhibitors. Kinetic studies on the non-toxic chromenotacrine CT6 showed that this compound behaves as a non-competitive inhibitor (Ki = 0.047 +/- 0.003 mu M), indicating that CT6 binds at the peripheral anionic site, a fact confirmed by molecular modeling analysis. In silica ADMET analysis showed also that CT6 should have a moderate BBB permeability. Consequently, non-toxic chromenotacrine CT6 can be considered as an attractive multipotent molecule for the potential treatment of AD. (C) 2014 Elsevier Masson SAS. All rights reserved.