N-(3,4-dihydro-6-hydroxy-2,2,5,7,8-pentamethyl-2H-1-benzopyran-4-yl)(diethylamino)acetamide | 389634-25-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(3,4-dihydro-6-hydroxy-2,2,5,7,8-pentamethyl-2H-1-benzopyran-4-yl)(diethylamino)acetamide
• 英文别名: 2-(diethylamino)-N-(6-hydroxy-2,2,5,7,8-pentamethyl-3,4-dihydrochromen-4-yl)acetamide
• CAS: 389634-25-7
• 化学式: C₂₀H₃₂N₂O₃
• 分子量: 348.486
• InChiKey: ISSAWACGRIFXMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-(3,4-dihydro-6-hydroxy-2,2,5,7,8-pentamethyl-2H-1-benzopyran-4-yl)bromoacetamide 、 二乙胺 以 甲苯 为溶剂， 以95%的产率得到N-(3,4-dihydro-6-hydroxy-2,2,5,7,8-pentamethyl-2H-1-benzopyran-4-yl)(diethylamino)acetamide
  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

• 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
• Bifunctional agents possessing antioxidant and antiarrhythmic activity
  申请人：——

  公开号：US20040259763A1

  公开（公告）日：2004-12-23

  The present invention relates to novel bifunctional agents possessing antioxidant and antiarrhytmic activity, methods for the synthesis of the same and their applications in treating ischemia-reperfusion injury, as well as a variety of disorders related to free radicals and/or arrhythmias. These bifunctional drugs should prefrentially segregate in the membrane and produce their antiarrhytmic effects while, at the same time, help in protecting the membrane lipids by scavenging free radicals. The present invention comprises compounds represented by Formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 are further defined. 1
• US7115657B2
  申请人：——

  公开号：US7115657B2

  公开（公告）日：2006-10-03
• 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.