14β-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and Related Opioids. Further Examples of Pseudoirreversible μ Opioid Receptor Antagonists

详细信息    查看全文

• 作者：Nick P.R. Nieland ; David Rennison ; Jillian H. Broadbear ; Lauren Purington ; James H. Woods ; John R. Traynor ; John W. Lewis ; Stephen M. Husbands
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：November 12, 2009
• 年：2009
• 卷：52
• 期：21
• 页码：6926-6930
• 全文大小：771K
• 年卷期：v.52,no.21(November 12, 2009)
• ISSN：1520-4804

文摘

14β-4′-Chlorocinnamoylaminodihydronormorphinone (2a), and analogues, are selective pseudoirreversible antagonists of the μ opioid receptor (MOR). The preparation of analogues with ethynic bonds, replacing the ethenic bond of 2a, is described. The new ligands, in mouse antinociceptive assays, had pseudoirreversible MOR antagonist activity, which, in the case of 8b was of longer duration than that of 2a. The related codeinone (9b) had only antagonist activity in vivo, in contrast to 2a’s codeinone equivalent 3a, which had potent antinociceptive activity.