Synthesis and Pharmacological Evaluation of Aminothiazolomorphinans at the Mu and Kappa Opioid Receptors
| Autor: | Wei Li, Shayla Russell, Elena H. Chartoff, John L. Neumeyer, Brian I. Knapp, Anna W. Sromek, Jean M. Bidlack, Brian A. Provencher |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Agonist Morphinan medicine.drug_class Molecular Conformation Receptors Opioid mu CHO Cells Pharmacology κ-opioid receptor Article Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Cricetulus Aminothiazole Opioid receptor Drug Discovery medicine Animals Humans Dose-Response Relationship Drug Receptors Opioid kappa Cyclorphan Stereoisomerism Rats Gtpγs binding Thiazoles Morphinans chemistry Opioid Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 56:8872-8878 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm401290y |
| Popis: | Previous studies with aminothiazolomorphinans suggested that this class of opioid ligands may be useful as a potential pharmacotherapeutic to decrease drug abuse. Novel aminothiazole derivatives of cyclorphan were prepared to evaluate a series of aminothiazolomorphinans with varying pharmacological properties at the κ opioid receptor (KOR) and μ opioid receptor (MOR). This study was focused on exploring the regioisomeric analogs with the aminothiazole on the C-ring of the morphinan skeleton. Receptor binding and [(35)S]GTPγS binding assays were used to characterize the affinity and pharmacological properties of the aminothiazolomorphinans. Intracranial self-stimulation (ICSS) was used to compare the effects of a representative aminothiazolomorphinan with the morphinan mixed-KOR/MOR agonist butorphan (MCL-101) on brain-stimulation reward. |
| Databáze: | OpenAIRE |
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