Opioid agonists and antagonists. 6,6-Hydrazi and 6-oximino derivatives of 14-hydroxymorphinones

Journal of Medicinal Chemistry
1984.0

Abstract

Naloxone (1a), naltrexone (1b), and oxymorphone (1c) were converted to the corresponding 6,6-diaziridines (4a-c), oximes (5a-c), and oxime O-methyl ethers (6a-c). The antagonist derivatives (R = CH2CH = CH2 and R = CH2-c-C3H7) were less active than the parent ketones in the tail-flick assay vs. morphine, by 2-10-fold, except for 6a, which was much less active. The agonist analogues (R = Me) were more active than morphine but less active than dihydromorphine in standard agonist assays. None were significantly longer in duration of action. Thus structural changes at the C-6 position to produce diaziridines, oximes, and oxime O-methyl ethers provide compounds retaining expected opioid activity.

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