5,7,8-trimethyl-3,4-dihydro-2H-1,4-benzoxazine | 1145873-72-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 5,7,8-trimethyl-3,4-dihydro-2H-1,4-benzoxazine
• CAS: 1145873-72-8
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: KTLFDMSYPFGKNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,7,8-trimethyl-3,4-dihydro-2H-1,4-benzoxazine 、 溴乙酰溴 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以72%的产率得到2-bromo-1-(5,7,8-trimethyl-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone
  参考文献：
  名称：

  5,7,8-Trimethyl-benzopyran and 5,7,8-Trimethyl-1,4-benzoxazine Aminoamide Derivatives as Novel Antiarrhythmics against Ischemia−Reperfusion Injury

  摘要：

  6-Hydroxy-5,7,8-trimethyl-benzopyran derivatives and 5,7,8-trimethyl-1,4-benzoxazine analogues substituted by the lidocaine pharmacophore aminoamide functionality at C4 of N4, respectively, were synthesized and evaluated against arrhythmias associated with ischemia-reperfusion injury. The antiarrhythmic effect of substitutents at positions C2 and C6 was examined. Six out of the 11 new derivatives, exhibited arrhythmia scores 1.0-1.3 versus the control (4.5 +/- 1.2), which was also reflected to the % premature beats (0.5-3.9), control (13.7 +/- 3.6). Selected compounds were further studied by a conventional microelectrode method. 2-diethylamino-1-(5,7,8-trimethyl-2-phenyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethanotic (50) and the trolox-inspired 4-(2-diethylamino-acetyl)-2,5,7,8-tetramethyl-3.4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester (62) Suppress reperfusion arrhythmias and reduce malondialdehyde (MDA) content, leading to a fast recovery of the heart after ischemia-reperfusion. They exhibit combined class IB and class III antiarrhythmic properties, which constitutes them as promising compounds for further studies because, due to their multichannel "amiodarone like" effect, less proarrhythmic complications can be expected.

  DOI：

  10.1021/jm801228h
• 作为产物：
  描述：

  2-硝基-3,5,6-三甲基苯酚 在 dimethyl sulfide borane 、 palladium 10% on activated carbon 、 氢气 、 四丁基碘化铵 、 caesium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 5,7,8-trimethyl-3,4-dihydro-2H-1,4-benzoxazine
  参考文献：
  名称：

  Regulation of the Escherichia coli AtoSC two component system by synthetic biologically active 5;7;8-trimethyl-1;4-benzoxazine analogues

  摘要：

  The Escherichia coli AtoSC two component system; upon acetoacetate induction; regulates the expression of the atoDAEB operon; through His -> Asp phopshotransfer; thus modulating important cellular processes. In this report the effect of seven 5,7,8-trimethyl-1,4-benzoxazine derivatives on the regulation of the E. coli AtoSC system was studied. The new compounds were tested for their effectiveness on the expression of the atoC and the regulated atoDAEB operon. The non-substituted 5,7,8-trimethyl-1,4-benzoxazine (4a), was the most potent inducer on atoC transcription; resulting in accumulation of AtoC protein. The induction of atoC by 4a was specific; since no effect was observed on the other genes of the system (atoS and atoDAEB). Moreover; compound 4a was shown to significantly up-regulate the in vitro kinase activity of the histidine kinase AtoS without altering the protein levels in the cell. Interestingly; this compound appeared to modulate the acetoacetate-mediated induction of the atoDAEB promoter by the AtoSC system. These data provide the first evidence for a differential modulator role of 5,7,8-trimethyl-1,4-benzoxazine; on the AtoSC two component system mediated signaling. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.029

文献信息

• Regulation of the Escherichia coli AtoSC two component system by synthetic biologically active 5;7;8-trimethyl-1;4-benzoxazine analogues
  作者：Panagiota S. Filippou、Eftychia N. Koini、Theodora Calogeropoulou、Panagiota Kalliakmani、Christos A. Panagiotidis、Dimitrios A. Kyriakidis

  DOI：10.1016/j.bmc.2011.06.029

  日期：2011.8

  The Escherichia coli AtoSC two component system; upon acetoacetate induction; regulates the expression of the atoDAEB operon; through His -> Asp phopshotransfer; thus modulating important cellular processes. In this report the effect of seven 5,7,8-trimethyl-1,4-benzoxazine derivatives on the regulation of the E. coli AtoSC system was studied. The new compounds were tested for their effectiveness on the expression of the atoC and the regulated atoDAEB operon. The non-substituted 5,7,8-trimethyl-1,4-benzoxazine (4a), was the most potent inducer on atoC transcription; resulting in accumulation of AtoC protein. The induction of atoC by 4a was specific; since no effect was observed on the other genes of the system (atoS and atoDAEB). Moreover; compound 4a was shown to significantly up-regulate the in vitro kinase activity of the histidine kinase AtoS without altering the protein levels in the cell. Interestingly; this compound appeared to modulate the acetoacetate-mediated induction of the atoDAEB promoter by the AtoSC system. These data provide the first evidence for a differential modulator role of 5,7,8-trimethyl-1,4-benzoxazine; on the AtoSC two component system mediated signaling. (C) 2011 Elsevier Ltd. All rights reserved.
• 5,7,8-Trimethyl-benzopyran and 5,7,8-Trimethyl-1,4-benzoxazine Aminoamide Derivatives as Novel Antiarrhythmics against Ischemia−Reperfusion Injury
  作者：Eftychia N. Koini、Panagiota Papazafiri、Athanasios Vassilopoulos、Maria Koufaki、Zoltán Horváth、István Koncz、László Virág、Gy J. Papp、Andràs Varró、Theodora Calogeropoulou

  DOI：10.1021/jm801228h

  日期：2009.4.23

  6-Hydroxy-5,7,8-trimethyl-benzopyran derivatives and 5,7,8-trimethyl-1,4-benzoxazine analogues substituted by the lidocaine pharmacophore aminoamide functionality at C4 of N4, respectively, were synthesized and evaluated against arrhythmias associated with ischemia-reperfusion injury. The antiarrhythmic effect of substitutents at positions C2 and C6 was examined. Six out of the 11 new derivatives, exhibited arrhythmia scores 1.0-1.3 versus the control (4.5 +/- 1.2), which was also reflected to the % premature beats (0.5-3.9), control (13.7 +/- 3.6). Selected compounds were further studied by a conventional microelectrode method. 2-diethylamino-1-(5,7,8-trimethyl-2-phenyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethanotic (50) and the trolox-inspired 4-(2-diethylamino-acetyl)-2,5,7,8-tetramethyl-3.4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester (62) Suppress reperfusion arrhythmias and reduce malondialdehyde (MDA) content, leading to a fast recovery of the heart after ischemia-reperfusion. They exhibit combined class IB and class III antiarrhythmic properties, which constitutes them as promising compounds for further studies because, due to their multichannel "amiodarone like" effect, less proarrhythmic complications can be expected.