Structure‐Activity Relationship of Oxygenated Morphinans. V. Narcotic agonist and antagonist activity in the 14‐hydroxymorphinan series. Preliminary communication

Abstract
The synthesis of several 14‐hydroxymorphinans, using oxymorphone (= 3, 14‐dihydroxy‐4,5‐epoxy‐N‐methylmorphinan‐6‐one, 1) as starting material, is described. The antinociceptive potency of the N‐methyl substituted 14‐hydroxy‐morphinans was determined. Thus, in order of antinociceptive potency, 14‐hydroxy‐4‐methoxy‐N‐methylmorphinan‐6‐one (5) >4,5‐epoxy‐14‐hydroxy‐N‐methyl‐morphinan‐6‐one (3)>4, 14‐dihydroxy‐N‐methylmorphinan‐6‐one (4)>14‐hydroxy‐4‐methoxy‐N‐methylmorphinan (11) ≈4, 14‐dihydroxy‐N‐methylmorphinan (12). The most potent compound in this series, 14‐hydroxy‐4‐methoxy‐N‐methyl‐morphinan‐6‐one (5), was found to have about six times the potency of morphine; it was equipotent with levorphanol.