Novel antiarrhythmic compounds with combined class IB and class III mode of action

P. Mátyus, Ildikó Varga, Tivadar Rettegi, Antal Simay, Nikolett Kállay, László Károlyházy, Ákos Kocsis, A. Varró, István Pénzes, J. Papp

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cardiac arrhythmias represent a major area of cardiovascular research, and for drug therapy, a large choice of antiarrhythmic agents have been available. However, clinical trials with antiarrhythmic drugs have recently indicated that serious side effects may considerably limit the use of various antiarrhythmic agents, in particular, for preventing arrhythmia-related mortality. Amiodarone with its complex mode of action, while exerting a strong and favorable antiarrhythmic action, posseses extracardiac untoward side effects originating from its chemical structure. In this paper, we report on our attempt to develop conceptually new, therapeutically valuable antiarrhythmic compounds, in which Class I/B and Class III features were combined into single molecules bearing no structural resemblance to amiodarone. Synthesis and pharmacological screening of series of N-(phenylalkyl)-N-(phenoxyalkyl)amines led us to discover some new promising compounds with the required dual mode of action. GYKI-16638, selected for further investigation, was also found to possess a remarkable in vivo antiarrhythmic effect, and it is now considered as a safe new antiarrhythmic drug candidate.

Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalCurrent Medicinal Chemistry
Volume11
Issue number1
DOIs
Publication statusPublished - 2004

Fingerprint

Amiodarone
Anti-Arrhythmia Agents
Cardiac Arrhythmias
Bearings (structural)
Drug therapy
Cardiovascular Agents
Amines
Screening
Clinical Trials
Pharmacology
Drug Therapy
Molecules
Mortality
Research
GYKI 16638

Keywords

  • Class I/B
  • Class III antiarrhythmics
  • Dual mode of action
  • GYKI 16638
  • N-(phenylalkyl)-N-(phenoxyalkyl)amines

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Novel antiarrhythmic compounds with combined class IB and class III mode of action. / Mátyus, P.; Varga, Ildikó; Rettegi, Tivadar; Simay, Antal; Kállay, Nikolett; Károlyházy, László; Kocsis, Ákos; Varró, A.; Pénzes, István; Papp, J.

In: Current Medicinal Chemistry, Vol. 11, No. 1, 2004, p. 61-69.

Research output: Contribution to journalArticle

Mátyus, P, Varga, I, Rettegi, T, Simay, A, Kállay, N, Károlyházy, L, Kocsis, Á, Varró, A, Pénzes, I & Papp, J 2004, 'Novel antiarrhythmic compounds with combined class IB and class III mode of action', Current Medicinal Chemistry, vol. 11, no. 1, pp. 61-69. https://doi.org/10.2174/0929867043456232
Mátyus, P. ; Varga, Ildikó ; Rettegi, Tivadar ; Simay, Antal ; Kállay, Nikolett ; Károlyházy, László ; Kocsis, Ákos ; Varró, A. ; Pénzes, István ; Papp, J. / Novel antiarrhythmic compounds with combined class IB and class III mode of action. In: Current Medicinal Chemistry. 2004 ; Vol. 11, No. 1. pp. 61-69.
@article{91046d7a2a0447af8bc6604ef2e97854,
title = "Novel antiarrhythmic compounds with combined class IB and class III mode of action",
abstract = "Cardiac arrhythmias represent a major area of cardiovascular research, and for drug therapy, a large choice of antiarrhythmic agents have been available. However, clinical trials with antiarrhythmic drugs have recently indicated that serious side effects may considerably limit the use of various antiarrhythmic agents, in particular, for preventing arrhythmia-related mortality. Amiodarone with its complex mode of action, while exerting a strong and favorable antiarrhythmic action, posseses extracardiac untoward side effects originating from its chemical structure. In this paper, we report on our attempt to develop conceptually new, therapeutically valuable antiarrhythmic compounds, in which Class I/B and Class III features were combined into single molecules bearing no structural resemblance to amiodarone. Synthesis and pharmacological screening of series of N-(phenylalkyl)-N-(phenoxyalkyl)amines led us to discover some new promising compounds with the required dual mode of action. GYKI-16638, selected for further investigation, was also found to possess a remarkable in vivo antiarrhythmic effect, and it is now considered as a safe new antiarrhythmic drug candidate.",
keywords = "Class I/B, Class III antiarrhythmics, Dual mode of action, GYKI 16638, N-(phenylalkyl)-N-(phenoxyalkyl)amines",
author = "P. M{\'a}tyus and Ildik{\'o} Varga and Tivadar Rettegi and Antal Simay and Nikolett K{\'a}llay and L{\'a}szl{\'o} K{\'a}rolyh{\'a}zy and {\'A}kos Kocsis and A. Varr{\'o} and Istv{\'a}n P{\'e}nzes and J. Papp",
year = "2004",
doi = "10.2174/0929867043456232",
language = "English",
volume = "11",
pages = "61--69",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - Novel antiarrhythmic compounds with combined class IB and class III mode of action

AU - Mátyus, P.

AU - Varga, Ildikó

AU - Rettegi, Tivadar

AU - Simay, Antal

AU - Kállay, Nikolett

AU - Károlyházy, László

AU - Kocsis, Ákos

AU - Varró, A.

AU - Pénzes, István

AU - Papp, J.

PY - 2004

Y1 - 2004

N2 - Cardiac arrhythmias represent a major area of cardiovascular research, and for drug therapy, a large choice of antiarrhythmic agents have been available. However, clinical trials with antiarrhythmic drugs have recently indicated that serious side effects may considerably limit the use of various antiarrhythmic agents, in particular, for preventing arrhythmia-related mortality. Amiodarone with its complex mode of action, while exerting a strong and favorable antiarrhythmic action, posseses extracardiac untoward side effects originating from its chemical structure. In this paper, we report on our attempt to develop conceptually new, therapeutically valuable antiarrhythmic compounds, in which Class I/B and Class III features were combined into single molecules bearing no structural resemblance to amiodarone. Synthesis and pharmacological screening of series of N-(phenylalkyl)-N-(phenoxyalkyl)amines led us to discover some new promising compounds with the required dual mode of action. GYKI-16638, selected for further investigation, was also found to possess a remarkable in vivo antiarrhythmic effect, and it is now considered as a safe new antiarrhythmic drug candidate.

AB - Cardiac arrhythmias represent a major area of cardiovascular research, and for drug therapy, a large choice of antiarrhythmic agents have been available. However, clinical trials with antiarrhythmic drugs have recently indicated that serious side effects may considerably limit the use of various antiarrhythmic agents, in particular, for preventing arrhythmia-related mortality. Amiodarone with its complex mode of action, while exerting a strong and favorable antiarrhythmic action, posseses extracardiac untoward side effects originating from its chemical structure. In this paper, we report on our attempt to develop conceptually new, therapeutically valuable antiarrhythmic compounds, in which Class I/B and Class III features were combined into single molecules bearing no structural resemblance to amiodarone. Synthesis and pharmacological screening of series of N-(phenylalkyl)-N-(phenoxyalkyl)amines led us to discover some new promising compounds with the required dual mode of action. GYKI-16638, selected for further investigation, was also found to possess a remarkable in vivo antiarrhythmic effect, and it is now considered as a safe new antiarrhythmic drug candidate.

KW - Class I/B

KW - Class III antiarrhythmics

KW - Dual mode of action

KW - GYKI 16638

KW - N-(phenylalkyl)-N-(phenoxyalkyl)amines

UR - http://www.scopus.com/inward/record.url?scp=9144220806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144220806&partnerID=8YFLogxK

U2 - 10.2174/0929867043456232

DO - 10.2174/0929867043456232

M3 - Article

C2 - 14754426

AN - SCOPUS:9144220806

VL - 11

SP - 61

EP - 69

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 1

ER -