Other morphinans and related structures

Numerous patents have appeared describing derivatives of 5 and 6 as potential PAMOR antagonists. With the exception of 5 and 6, there are no peer-reviewed publications on structure-activity relationships, in vivo activity, or other preclinical data for the new agents. As viewed from the patent literature, introduction of polar substitutents into the morphinan scaffold is the preferred peripheralization strategy. 

Analogs 11-13 are representative of new morphinan-derived zwitter-ions. The orally active 14-substituted ether (11) is 10-fold more potent than 2 in reversing morphine-induced decrease in GI motility in rat [41]. 

No biological data was reported for 12 [42] and 13 [43] or for a series of the 6,7-unsaturated-7-carbamoyl morphinans represented by 14 [44]. 

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