5,7,8-trimethyl-benzopyran and 5,7,8-trimethyl-1,4-benzoxazine aminoamide derivatives as novel antiarrhythmics against ischemia-reperfusion injury

Eftychia N. Koini, Panagiota Papazafiri, Athanasios Vassilopoulos, Maria Koufaki, Zoltán Horváth, István Koncz, László Virág, Gy J. Papp, Andràs Varró, Theodora Calogeropoulou

Research output: Article

40 Citations (Scopus)

Abstract

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 or 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)-ethanone (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.

Original languageEnglish
Pages (from-to)2328-2340
Number of pages13
JournalJournal of Medicinal Chemistry
Volume52
Issue number8
DOIs
Publication statusPublished - ápr. 23 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of '5,7,8-trimethyl-benzopyran and 5,7,8-trimethyl-1,4-benzoxazine aminoamide derivatives as novel antiarrhythmics against ischemia-reperfusion injury'. Together they form a unique fingerprint.

  • Cite this