Abstract
We previously reported the discovery of diphenylimidazoles as potent sodium channel blockers, potentially useful in the treatment of epilepsy. In this work we further explore the structural requirements necessary for the potency of these derivatives with the aim to understand which structural modifications of the original scaffold could be tolerated in order to retain activity. We have synthesized new compounds working on the 2-position of the imidazole ring. First we have introduced a carbonyl spacer, that was subsequently reduced to alcohol. Both carbonyl and alcohol derivatives have been tested for their ability to block NaV1.6 sodium channel subtype in vitro and for their antiepileptic activity in rodent acute seizures models.
Keywords: Sodium channels, patch clamp electrophysiology, NaV1.6, Phenyl-imidazoles.
Letters in Drug Design & Discovery
Title:Sodium Channel Blocking Activity and In-vivo Testing of New Phenylimidazole Derivatives
Volume: 13 Issue: 9
Author(s): Mirko Rivara, Manoj K. Patel, Alberto Rapalli and Valentina Zuliani
Affiliation:
Keywords: Sodium channels, patch clamp electrophysiology, NaV1.6, Phenyl-imidazoles.
Abstract: We previously reported the discovery of diphenylimidazoles as potent sodium channel blockers, potentially useful in the treatment of epilepsy. In this work we further explore the structural requirements necessary for the potency of these derivatives with the aim to understand which structural modifications of the original scaffold could be tolerated in order to retain activity. We have synthesized new compounds working on the 2-position of the imidazole ring. First we have introduced a carbonyl spacer, that was subsequently reduced to alcohol. Both carbonyl and alcohol derivatives have been tested for their ability to block NaV1.6 sodium channel subtype in vitro and for their antiepileptic activity in rodent acute seizures models.
Export Options
About this article
Cite this article as:
Rivara Mirko, Patel K. Manoj, Rapalli Alberto and Zuliani Valentina, Sodium Channel Blocking Activity and In-vivo Testing of New Phenylimidazole Derivatives, Letters in Drug Design & Discovery 2016; 13 (9) . https://dx.doi.org/10.2174/1570180813666160714125755
DOI https://dx.doi.org/10.2174/1570180813666160714125755 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- 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
Related Articles
-
Serotonin<sub>2c</sub> Receptor Constitutive Activity: In vivo Direct and Indirect Evidence and Functional Significance
Central Nervous System Agents in Medicinal Chemistry Anticonvulsant Sulfonamides/Sulfamates/Sulfamides with Carbonic Anhydrase Inhibitory Activity: Drug Design and Mechanism of Action
Current Pharmaceutical Design Journey Describing the Cytotoxic Potential of Withanolides: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery Interactions between Ketamine and Magnesium for the Treatment of Pain: Current State of the Art
CNS & Neurological Disorders - Drug Targets Zinc-Permeable Ion Channels: Effects on Intracellular Zinc Dynamics and Potential Physiological/Pathophysiological Significance
Current Medicinal Chemistry 5 Hz Repetitive Transcranial Magnetic Stimulation with Maximum Voluntary Muscle Contraction Facilitates Cerebral Cortex Excitability of Normal Subjects
CNS & Neurological Disorders - Drug Targets Reacting to Stress: Radical Cellular Pathways for Novel Drug Development
Current Neurovascular Research Development of Nitrile-Based Peptidic Inhibitors of Cysteine Cathepsins
Current Topics in Medicinal Chemistry Transdermal Drug Delivery: A Step towards Treatment of Cancer
Recent Patents on Anti-Cancer Drug Discovery From Cannabis to Cannabidiol to Treat Epilepsy, Where Are We?
Current Pharmaceutical Design Antiepileptic Treatments in Developing Countries
Current Pharmaceutical Design Editorial
Current Medical Imaging Combination Therapy for Multi-Target Manipulation of Secondary Brain Injury Mechanisms
Current Neuropharmacology Inhibitors of Multidrug Efflux Transporters: Their Membrane and Protein Interactions
Mini-Reviews in Medicinal Chemistry Tactile Angle Discrimination Decreases due to Subjective Cognitive Decline in Alzheimer’s Disease
Current Alzheimer Research Pharmacological Management of Huntingtons Disease: An Evidence- Based Review
Current Pharmaceutical Design Obesity Pharmacotherapy: Current Perspectives and Future Directions
Current Cardiology Reviews MiR-125a-5p Alleviates Dysfunction and Inflammation of Pentylenetetrazol- induced Epilepsy Through Targeting Calmodulin-dependent Protein Kinase IV (CAMK4)
Current Neurovascular Research Neurocysticercosis: The Enigmatic Disease
Central Nervous System Agents in Medicinal Chemistry Venoms and Poisonings during the Centuries: A Narrative Review
Endocrine, Metabolic & Immune Disorders - Drug Targets