Narcotic antagonists. 4. Carbon-6 derivatives of N-substituted noroxymorphones as narcotic antagonists

Abstract

A series of new narcotic antagonists has been synthesized by modifying the C-6 carbonyl group in naloxone (Ia) and naltrexone (Ib). New functional units were introduced by reaction with various phosphorus and sulfur ylides and alkyllithium reagents. The activity of the new compounds were measured by the hot-plate and tail-clip tests after oral administration to mice. The majority of the new narcotic antagonists exhibited oral potencies considerably superior to the parent compounds, with 6-methylene derivatives IIa and IIb showing the most impressive increases.