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
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
-
Pyrimidine-fused Derivatives: Synthetic Strategies and Medicinal Attributes
Current Topics in Medicinal Chemistry Preclinical Evaluation of a Zinc Finger Inhibitor Targeting Lentivirus Nucleocapsid Protein in SIV-Infected Monkeys
Current HIV Research Deep Sequencing Approaches to Antibody Discovery
Current Drug Discovery Technologies Pneumonia in the Burn Patient
Current Respiratory Medicine Reviews New Features that Improve the Pharmacophore Tools from Accelrys
Current Computer-Aided Drug Design The Lung in Sepsis: Guilty or Innocent?
Endocrine, Metabolic & Immune Disorders - Drug Targets Peptide Drugs QSAR Modeling Based on a New Descriptor of Amino Acids- SVGT
Letters in Drug Design & Discovery Development and Current Status of Unconventional Platinum Anticancer Complexes
Mini-Reviews in Medicinal Chemistry Depression Discovery in Covid-19 Communities Using Deep Learning
Recent Patents on Engineering Functional Antagonism between NF-κB and Nuclear Receptors: Implications in Carcinogenesis and Strategies for Optimal Cancer Chemopreventive Interventions
Current Cancer Drug Targets 4-Anilino-3-quinolinecarbonitriles: An Emerging Class of Kinase Inhibitors - An Update
Medicinal Chemistry Reviews - Online (Discontinued) Identification of Novel Inhibitors of SARS-CoV-2 Mpro from NCI Database by a Drug Repurposing Approach
Current Chinese Chemistry China Coronavirus Outbreak: All the Latest Updates
Current Topics in Medicinal Chemistry The Docking Based 3D-QSAR Studies on Isoindolinone Derived Inhibitors of p53-MDM2 Binding
Letters in Drug Design & Discovery Recent Advances in Pulmonary Hypertension Therapy
Recent Patents on Cardiovascular Drug Discovery Recent Patents on Mesenchymal Stem Cell Mediated Therapy in Inflammatory Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Antibody-drug Conjugate Targets, Drugs, and Linkers
Current Cancer Drug Targets The Plastic and Functional Changes in Hippocampal Neurons During Pregnancy, Delivery and Postpartum are Reversed by Offspring Deprivation
Current Psychopharmacology Advances in Research of Schiff-Base Metal Complexes as Potent Antioxidants
Current Medicinal Chemistry Efficacy of Lopinavir/Ritonavir Compared With Standard Care for Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review
Infectious Disorders - Drug Targets