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, class III antiarrhythmics, dual mode of action, n-(phenylalkyl)-n-(phenoxyalkyl)amines, gykI 16638
Current Medicinal Chemistry
Title: Novel Antiarrhythmic Compounds with Combined Class IB and Class III Mode of Action
Volume: 11 Issue: 1
Author(s): Peter Matyus, Ildiko Varga, Tivadar Rettegi, Antal Simay, Nikolett Kallay, Laszlo Karolyhazy, Akos Kocsis, Andras Varro, Istvan Penzes and Julius Gy. Papp
Affiliation:
Keywords: class, class III antiarrhythmics, dual mode of action, n-(phenylalkyl)-n-(phenoxyalkyl)amines, gykI 16638
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.
Export Options
About this article
Cite this article as:
Matyus Peter, Varga Ildiko, Rettegi Tivadar, Simay Antal, Kallay Nikolett, Karolyhazy Laszlo, Kocsis Akos, Varro Andras, Penzes Istvan and Papp Gy. Julius, Novel Antiarrhythmic Compounds with Combined Class IB and Class III Mode of Action, Current Medicinal Chemistry 2004; 11 (1) . https://dx.doi.org/10.2174/0929867043456232
DOI https://dx.doi.org/10.2174/0929867043456232 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Editorial [Hot Topic: Membrane Channels as Therapeutic Targets (Executive Editor: Jean-Claude Herve)]
Current Pharmaceutical Design Genomic and Non-genomic Effects of Aldosterone
Current Signal Transduction Therapy Generic Clopidogrel Besylate in the Secondary Prevention of Atherothrombotic Events: A 6-month Follow-up of a Randomised Clinical Trial
Current Vascular Pharmacology Micro-RNA in Disease and Gene Therapy
Current Drug Discovery Technologies Antitumoral-Lipid-Based Nanoparticles: a Platform for Future Application in Osteosarcoma therapy
Current Pharmaceutical Design Non-Respiratory Manifestations of COVID-19 and Pathophysiological Evidences
New Emirates Medical Journal Investigating Drug-induced Mitochondrial Toxicity: A Biosensor to Increase Drug Safety?
Current Drug Safety Novel Stereoselective Oximes: Their Synthesis and Anti-leishmanials Evaluation
Current Bioactive Compounds The Control of Arterial Hypertension: Epidemiological and Economic Challenge
Current Hypertension Reviews Efficacy and Safety of Mesenchymal Stromal Cells Therapy for COVID-19 Infection: A Systematic Review and Meta-analysis
Current Stem Cell Research & Therapy Tuning hERG Out: Antitarget QSAR Models for Drug Development
Current Topics in Medicinal Chemistry Possible Exploitation of Non-Neuronal and Non-Chemical Synaptic Signalling Pathways in Epilepsy Therapy
Current Signal Transduction Therapy New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases
Current Medicinal Chemistry Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart
Current Pharmaceutical Biotechnology Cardiac Amyloid - A Hidden Contributor to Cardiac Dysfunction Following Cardiac Surgery: Case Report and Literature Review
Current Cardiology Reviews Antioxidative Effects of Rhodiola Genus: Phytochemistry and Pharmacological Mechanisms against the Diseases
Current Topics in Medicinal Chemistry The Role of Continuous Positive Airway Pressure in the Treatment of Hypertension in Patients with Obstructive Sleep Apnea-Hypoapnea Syndrome: A Review of Randomized Trials
Reviews on Recent Clinical Trials The Right Ventricle: Biologic Insights and Response to Disease: Updated
Current Cardiology Reviews Modulators of Ion Channels Activated by Hypotonic Swelling in Cardiomyocytes: New Perspectives for Pharmacological Treatment of Life-Threatening Arrhythmias
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Tissue Engineering Techniques in Cardiac Repair and Disease Modelling
Current Pharmaceutical Design