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In an effort to develop opiate receptor-site-directed alkylating agents, a series of 3-hydroxy-17-aralkylmorphinans containing reactive groups was synthesized and tested for analgesic and opiate antagonist activity. Many of the target compounds exhibited the characteristics of agonists and, among this group, some were found to be active blockers of morphine analgesia. One of the more potent antagonists (41) was investigated further and it was found that while its action is specifically associated with opiate receptors, 41 could not be classified either as a competitive or noncompetitive antagonist in the classical sense. The duration of antagonist action in vivo of 41 and its in vitro receptor binding characteristics suggest that covalent association with opiate receptors is not not an important factor.

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