3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-carboxaldehyde | 389633-98-1

• 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: 3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-carboxaldehyde
• 英文别名: 3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5-carboxaldehyde；6-Methoxy-2,2,7,8-tetramethyl-3,4-dihydrochromene-5-carbaldehyde
• CAS: 389633-98-1
• 化学式: C₁₅H₂₀O₃
• 分子量: 248.322
• InChiKey: IKWOZIUYYOKFIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-carboxaldehyde 在 乙酸铵 、 lithium aluminium tetrahydride 、 甲酸 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 30.0h， 生成 N-methyl-N-[2-(4-nitrophenoxy)ethyl]-2-(3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5-yl)ethylamine
  参考文献：
  名称：

  Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores

  摘要：

  We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 mu M concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5-yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.065
• 作为产物：
  描述：

  2,2,7,8-四甲基-6-色满醇 在 四氯化钛 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 10.0h， 生成 3,4-dihydro-6-methoxy-2,2,7,8-tetramethyl-2H-benzopyran-5-carboxaldehyde
  参考文献：
  名称：

  Bifunctional agents for reperfusion arrhythmias: Novel hybrid vitamin E/Class I antiarrhythmics

  摘要：

  We have synthesized a series of hybrid compounds combining the pharmacophoric redox moieties of vitamin E and key features responsible for the antiarrhythmic properties of the class I antiarrhythmics procainamide and lidocaine. Procainamide analogue (2a) and lidocaine analogues (14a) and (14b) are very strong inhibitors of lipid peroxidation. All analogues tested at 100 or 30 muM enhanced the post ischemic recovery without inducing ventricular fibrillations while there was no evidence in our experiments for drug-induced pro-arrhythmia. In addition, they induced a widening of the QRS intervals. Our data suggest that the efficacy of the new compounds in preventing reperfusion arrhythmias could be attributed to their combined effects involving inhibition of free radical mediated damage coupled with antiarrhythmic properties. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.08.010

文献信息

• Hybrid-Increased Radical-Scavenging Activity of Resveratrol Derivatives by Incorporating a Chroman Moiety of Vitamin E
  作者：Jie Yang、Guo-Yun Liu、Dong-Liang Lu、Fang Dai、Yi-Ping Qian、Xiao-Ling Jin、Bo Zhou

  DOI：10.1002/chem.201002020

  日期：2010.11.15

  A winning combination: Resveratrol derivatives incorporating a chroman moiety of vitamin E were constructed, resulting in the remarkable enhancement in tris(2,4,6‐trichloro‐3,5‐dinitrophenyl)methyl radical (HNTTM.)‐scavenging activity as compared with the parent molecules (see scheme). Reaction kinetic analysis, oxidative product identification, and redox potential determination demonstrate that the

  一个成功的组合：构建了一种白藜芦醇衍生物，其中掺入了维生素E的苯并二氢吡喃部分，与三（2,4,6-三氯-3,5-二硝基苯基）甲基自由基（HNTTM 。）相比，清除活性显着提高。母体分子（参见方案）。反应动力学分析，氧化产物鉴定和氧化还原电势测定表明，该反应受顺序质子损失电子转移（SPLET）机制控制。
• Chroman/Catechol Hybrids:  Synthesis and Evaluation of Their Activity against Oxidative Stress Induced Cellular Damage
  作者：Maria Koufaki、Elissavet Theodorou、Dimitrios Galaris、Lambros Nousis、Efrosini S. Katsanou、Michael N. Alexis

  DOI：10.1021/jm0506120

  日期：2006.1.1

  chromans substituted at positions 2 or 5 by catechol derivatives were synthesized, and their activity against oxidative stress induced cellular damage was studied. Specifically, the ability of the new molecules to protect cultured cells from H(2)O(2)-induced DNA damage was evaluated using single cell gel electrophoresis (comet assay), while the neuroprotective activity of the new compounds against oxidative

  合成了三类在邻苯二酚衍生物在2或5位取代的苯并二氢吡喃，并研究了它们对氧化应激诱导的细胞损伤的活性。具体来说，使用单细胞凝胶电泳（彗星试验）评估了新分子保护培养的细胞免受H（2）O（2）诱导的DNA损伤的能力，而新化合物针对氧化应激诱导的神经保护活性被编程使用谷氨酸-challanged海马HT22细胞研究了细胞死亡。大多数新化合物比槲皮素具有更强的神经保护作用。5-取代的苯并二氢吡喃类似物，例如咖啡酰胺12和16和二氢二苯乙烯类似物24，分别对Jurkat T细胞和HT22细胞中H（2）O（2）-和谷氨酸诱导的损伤最有效。
• Synthesis of chroman analogues of lipoic acid and evaluation of their activity against reperfusion arrhythmias
  作者：Maria Koufaki、Anastasia Detsi、Elissavet Theodorou、Christina Kiziridi、Theodora Calogeropoulou、Athanasios Vassilopoulos、Angeliki P. Kourounakis、Eleni Rekka、Panos N. Kourounakis、Catherine Gaitanaki、Panagiota Papazafiri

  DOI：10.1016/j.bmc.2004.07.012

  日期：2004.9

  Novel hybrids of lipoic acid and trolox connected through triamine spacers as well as analogues in which the lipoic acid was attached at different positions of the chroman moiety of vitamin E through an amide bond, were synthesized and exhibited strong inhibition of the microsomal lipid peroxidation. Moreover, the new molecules, at 1 muM concentration, reduced reperfusion arrhythimas and MDA content on isolated rat heart preparations, with the 2- and 5-subtituted chromans possessing the better cardioprotective activity. (C) 2004 Elsevier Ltd. All rights reserved.
• Design and synthesis of novel neuroprotective 1,2-dithiolane/chroman hybrids
  作者：Maria Koufaki、Christina Kiziridi、Xanthippi Alexi、Michael N. Alexis

  DOI：10.1016/j.bmc.2009.07.010

  日期：2009.9.1

  Novel 1,2-dithiolane/chroman hybrids bearing heterocyclic rings such as 1,2,4- and 1,3,4-oxadiazole, 1,2,3-triazole and tetrazole were designed and synthesized. The neuroprotective activity of the new analogues was tested against oxidative stress-induced cell death of glutamate-challenged HT22 hippocampal neurons. Our results show that bioisosteric replacement of amide group in 2-position of the chroman moiety, by 1,3,4- oxadiazole did not affect activity. However, analogue 5 bearing the 1,2,4- oxadiazole moiety showed improved neuroprotective activity. The presence of nitrogen heterocycles strongly influences the neuroprotective activity of 5-substituted chroman derivatives, depending on the nature of heterocycle. Replacement of the amide group of the first generation analogues by 1,2,4- oxadiazole or 1,2,3-triazole resulted in significant improvement of the activity against glutamate induced oxidative stress. (C) 2009 Elsevier Ltd. All rights reserved.
• BIFUNCTIONAL AGENTS POSSESSING ANTIOXIDANT AND ANTIARRHYTHMIC ACTIVITY
  申请人：Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A.

  公开号：EP1301504B1

  公开（公告）日：2004-11-03