Synthesis and Pharmacological Evaluation of Aminothiazolomorphinans at the Mu and Kappa Opioid Receptors

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• 作者：Brian A. Provencher ; Anna W. Sromek ; Wei Li ; Shayla Russell ; Elena Chartoff ; Brian I. Knapp ; Jean M. Bidlack ; John L. Neumeyer
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：November 14, 2013
• 年：2013
• 卷：56
• 期：21
• 页码：8872-8878
• 全文大小：354K
• 年卷期：v.56,no.21(November 14, 2013)
• ISSN：1520-4804

文摘

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 魏 opioid receptor (KOR) and 渭 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 [³⁵S]GTP纬S 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.