6-chloro-2,5,7,8-tetramethyl-3-thioxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester | 1145873-97-7

• 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: 6-chloro-2,5,7,8-tetramethyl-3-thioxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester
• 英文别名: ethyl 6-chloro-2,5,7,8-tetramethyl-3-sulfanylidene-4H-1,4-benzoxazine-2-carboxylate
• CAS: 1145873-97-7
• 化学式: C₁₅H₁₈ClNO₃S
• 分子量: 327.832
• InChiKey: PCJXEXBNVHSRLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  79.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-2,5,7,8-tetramethyl-3-thioxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester 在 镍 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 以81%的产率得到6-chloro-2,5,7,8-tetramethyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester
  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：

  6-chloro-2,5,7,8-tetramethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以98%的产率得到6-chloro-2,5,7,8-tetramethyl-3-thioxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester
  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

文献信息

• 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.