Abstract
Since the pioneering studies of Fleckenstein and co-workers, L-Type Calcium Channel (LTCC) blockers have attracted large interest due to their effectiveness in treating several cardiovascular diseases. Medicinal chemists achieved high potency and tissue selectivity by decorating the 1-4-DHP nucleus, the most studied scaffold among LTCC blockers. Nowadays it is clear that the 1,4-DHP nucleus is a privileged scaffold since, when appropriately substituted, it can selectively modulate diverse receptors, channels and enzymes. Therefore, the 1,4-DHP scaffold could be used to treat various diseases by a single-ligand multi-target approach. In this review, we describe the structure-activity relationships of 1,4-DHPs at ion channels, G-protein coupled receptors, and outline the potential for future therapeutic applications.
Keywords: 1,4-Dihydropyridines, 4-DHPs, 1,4-Dihydropyridine scaffold, Ion Channels, G-protein coupled receptors, modulators, therapeutic applications, multi-target ligand, Voltage-Gated Calcium Channels, Ligand-Gated Ion Channels, Calcium antagonists, L-Type Calcium Channel blockers
Current Medicinal Chemistry
Title: 1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives (Part 1): Action in Ion Channels and GPCRs
Volume: 18 Issue: 32
Author(s): P. Ioan, E. Carosati, M. Micucci, G. Cruciani, F. Broccatelli, B. S. Zhorov, A. Chiarini and R. Budriesi
Affiliation:
Keywords: 1,4-Dihydropyridines, 4-DHPs, 1,4-Dihydropyridine scaffold, Ion Channels, G-protein coupled receptors, modulators, therapeutic applications, multi-target ligand, Voltage-Gated Calcium Channels, Ligand-Gated Ion Channels, Calcium antagonists, L-Type Calcium Channel blockers
Abstract: Since the pioneering studies of Fleckenstein and co-workers, L-Type Calcium Channel (LTCC) blockers have attracted large interest due to their effectiveness in treating several cardiovascular diseases. Medicinal chemists achieved high potency and tissue selectivity by decorating the 1-4-DHP nucleus, the most studied scaffold among LTCC blockers. Nowadays it is clear that the 1,4-DHP nucleus is a privileged scaffold since, when appropriately substituted, it can selectively modulate diverse receptors, channels and enzymes. Therefore, the 1,4-DHP scaffold could be used to treat various diseases by a single-ligand multi-target approach. In this review, we describe the structure-activity relationships of 1,4-DHPs at ion channels, G-protein coupled receptors, and outline the potential for future therapeutic applications.
Export Options
About this article
Cite this article as:
Ioan P., Carosati E., Micucci M., Cruciani G., Broccatelli F., S. Zhorov B., Chiarini A. and Budriesi R., 1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives (Part 1): Action in Ion Channels and GPCRs, Current Medicinal Chemistry 2011; 18 (32) . https://dx.doi.org/10.2174/092986711797535173
DOI https://dx.doi.org/10.2174/092986711797535173 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Cardiac Side Effects of Chemotherapy: State of Art and Strategies for a Correct Management
Current Vascular Pharmacology D-allose: Molecular Pathways and Therapeutic Capacity in Cancer
Current Molecular Pharmacology Recent Developments of Melatonin Related Antioxidant Compounds
Combinatorial Chemistry & High Throughput Screening Targeting COVID-19 in Parkinson’s Patients: Drugs Repurposed
Current Medicinal Chemistry Exploring Mode of Phosphoramidon and Aβ Peptide Binding to hECE-1 by Molecular Dynamics and Docking Studies
Protein & Peptide Letters New Ligands of the Tubulin Colchicine Site Based on X-Ray Structures
Current Topics in Medicinal Chemistry Aminoimidazo[1,2-a]pyridine Bearing Different Pyrazole Moieties as the Structural Scaffold for the Development of BACE1 Inhibitor; Synthesis, Structural Characterization, <i>in vitro</i> and <i>in silico</i> Studies
Current Organic Synthesis A Review of Recent Advancements in Anti-tubercular Molecular Hybrids
Current Medicinal Chemistry Diabetes Mellitus during the Pandemic Covid-19: Prevalence, Pathophysiology, Mechanism, and Management: An updated overview
Current Diabetes Reviews MraY Inhibitors as Novel Antibacterial Agents
Current Topics in Medicinal Chemistry α-Secretase in Alzheimers Disease and Beyond: Mechanistic, Regulation and Function in the Shedding of Membrane Proteins
Current Alzheimer Research Targeting Cardiomyocyte Ca<sup>2+</sup> Homeostasis in Heart Failure
Current Pharmaceutical Design Pharmacophore Discovery - Lessons Learned
Current Pharmaceutical Design Foreword
Coronaviruses Synthesis, Characterization and Theoretical Studies of Novel Phosphonates as uPA Inhibitors
Current Organic Chemistry Recent Process in the Inhibitors of UDP-3-O-(R-3-hydroxyacyl)-Nacetylglucosamine Deacetylase (LpxC) Against Gram-Negative Bacteria
Mini-Reviews in Medicinal Chemistry Soluble Diphtheria Toxin Variant, CRM 197 was Obtained in <i>Escherichia coli</i> at High Productivity Using SUMO Fusion and an Adjusted Expression Strategy
Protein & Peptide Letters Synthesis, Antifungal Evaluation and Molecular Docking Studies on 2- thioxoimidazolidin-4-one Derivatives
Medicinal Chemistry Clinical Spectrum, Geographical Variability of COVID-19, and its Implications
Coronaviruses Systems Biology: A New Tool for Farm Animal Science
Current Protein & Peptide Science