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14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists.

ABSTRACT: 14beta-4'-Chlorocinnamoylaminodihydronormorphinone (2a), and analogues, are selective pseudoirreversible antagonists of the mu 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.

SUBMITTER: Nieland NP

PROVIDER: S-EPMC2788771 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists.

Nieland Nick P R NP Rennison David D Broadbear Jillian H JH Purington Lauren L Woods James H JH Traynor John R JR Lewis John W JW Husbands Stephen M SM

Journal of medicinal chemistry 20091101 21

14beta-4'-Chlorocinnamoylaminodihydronormorphinone (2a), and analogues, are selective pseudoirreversible antagonists of the mu 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 codei ...[more]

PMID: 19842669

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