| abstract |
Intramolecular cyclization resulting in the formation of cyclic urea, carbamate, or thiocarbamate provides patients with controlled release of phenolic opioids using prodrugs that can release phenolic opioids upon enzyme activation how to. Specifically, this method comprises administering to said patient a corresponding compound substituted with a spacer leaving group having a nitrogen nucleophilic group in which the phenolic hydrogen atom is protected with an enzymatically cleavable moiety. The arrangement of the spacer leaving group and the nitrogen nucleophilic group is such that upon enzymatic cleavage of the cleavable moiety, the nitrogen nucleophilic group can form a cyclic urea, carbamate or thiocarbamate, The arrangement is such that the compound is released to the patient from the spacer leaving group to provide controlled release of the phenolic opioid. |