Abstract
Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics. This study was aimed to review the structure-activity-relationship (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine ring. Pharmacological results show that the groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor alone (i.e. voluminosity of the group and cis/trans isomerism), rather than the polarity and/or chemical reactivity, plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that the introduction of a functional group such as 3-carbomethoxy reduces the duration of action by altering pharmacokinetic properties. SAR findings obtained by evaluating the neurotoxic effects of fentanyl analogs substituted in the position 3 of the piperidine ring parallel the SAR findings on analgesia in regard to potency and duration of action. This might suggest that similar receptors are involved in producing both antinociceptive and neurotoxic effects of these drugs. It appears that both the potency and the duration of action in the series of fentanyl analogs substituted in position 4 of the piperidine ring is influenced only by the steric requirement and not by the chemical nature of the substituent.
Keywords: Fentanyl, analogs, structure-activity-relationship (SAR), analgesic activity, neurotoxicity
Current Medicinal Chemistry
Title: Fentanyl Analogs: Structure-Activity-Relationship Study
Volume: 16 Issue: 19
Author(s): S. Vuckovic, M. Prostran, M. Ivanovic, Lj. Dosen-Micovic, Z. Todorovic, Z. Nesic, R. Stojanovic, N. Divac and Z. Mikovic
Affiliation:
Keywords: Fentanyl, analogs, structure-activity-relationship (SAR), analgesic activity, neurotoxicity
Abstract: Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics. This study was aimed to review the structure-activity-relationship (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine ring. Pharmacological results show that the groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor alone (i.e. voluminosity of the group and cis/trans isomerism), rather than the polarity and/or chemical reactivity, plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that the introduction of a functional group such as 3-carbomethoxy reduces the duration of action by altering pharmacokinetic properties. SAR findings obtained by evaluating the neurotoxic effects of fentanyl analogs substituted in the position 3 of the piperidine ring parallel the SAR findings on analgesia in regard to potency and duration of action. This might suggest that similar receptors are involved in producing both antinociceptive and neurotoxic effects of these drugs. It appears that both the potency and the duration of action in the series of fentanyl analogs substituted in position 4 of the piperidine ring is influenced only by the steric requirement and not by the chemical nature of the substituent.
Export Options
About this article
Cite this article as:
Vuckovic S., Prostran M., Ivanovic M., Dosen-Micovic Lj., Todorovic Z., Nesic Z., Stojanovic R., Divac N. and Mikovic Z., Fentanyl Analogs: Structure-Activity-Relationship Study, Current Medicinal Chemistry 2009; 16 (19) . https://dx.doi.org/10.2174/092986709788682074
DOI https://dx.doi.org/10.2174/092986709788682074 |
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
-
Recent Progress in Biological Activities and Synthetic Methodologies of Pyrroloquinoxalines
Mini-Reviews in Medicinal Chemistry Recent Advances in Antiviral Activity of Benzo/Heterothiadiazine Dioxide Derivatives
Current Medicinal Chemistry Reversal of ABC Drug Transporter-Mediated Multidrug Resistance in Cancer Cells: Evaluation of Current Strategies
Current Molecular Pharmacology Outlining the Molecules Tested <i>In Vivo</i> for Chagas Disease, Malaria, and Schistosomiasis Over the Last Six Years - A Literature Review Focused on New Synthetic Drug Identities and Repurposing Strategies
Current Medicinal Chemistry Proteomic Studies on Plant-Pathogen Interaction in Compatible and Incompatible Systems
Current Proteomics Overview of Drug Therapy of COVID-19 with Safety and the Potential Clinical Benefits
Current Drug Therapy Recent Developments in Macrolide Antimicrobial Research
Current Topics in Medicinal Chemistry Advances in the Structure-Based Design of the Influenza A Neuraminidase Inhibitors
Current Drug Targets Clinical and Marketed Proteasome Inhibitors for Cancer Treatment
Current Medicinal Chemistry Neurological Complications in COVID-19 Patients and its Implications for Associated Mortality
Current Neurovascular Research A Comparative Study of SARS, MERS with COVID-19
Coronaviruses A Mechanistic Review on Plant-derived Natural Inhibitors of Human Coronaviruses with Emphasis on SARS-COV-1 and SARS-COV-2
Current Drug Targets A Clinically Validated, Broadly Active, Oral Viral Superinfection Therapy Could Mitigate Symptoms in Early-stage COVID-19 Patients
Infectious Disorders - Drug Targets Integrating Virtual Screening Methods to the Quest for Novel Membrane Protein Ligands
Current Medicinal Chemistry - Central Nervous System Agents Diselenides and Selenocyanates as Versatile Precursors for the Synthesis of Pharmaceutically Relevant Compounds
Current Organic Synthesis Ligand- and Protein-Based Modeling Studies of the Inhibitors of Human Cytochrome P450 2D6 and a Virtual Screening for Potential Inhibitors from the Chinese Herbal Medicine, Scutellaria baicalensis (Huangqin,Baikal Skullcap)
Combinatorial Chemistry & High Throughput Screening Synthesis and Evaluation of Compounds Containing 4-arylpiperazinyl Moieties Linked to a 2-(pyridin-3-yl)-1H-benzimidazole as p38 MAP Kinase Inhibitors
Letters in Drug Design & Discovery COVID-19 Associated Acute Pancreatitis: A Case Series from India
Infectious Disorders - Drug Targets Inflammatory Cytokines in Acute Ischemic Stroke
Current Pharmaceutical Design A Therapeutic Journey of 5-Pyrazolones as a Versatile Scaffold: A Review
Mini-Reviews in Medicinal Chemistry