ABSTRACT
The little compound 1a has been prepared and was found to be a strong, orally active agonist with narcotic--antagonist properties. 1a was prepared by two independent routes: (1) nitration of volazocine and subsequent reduction and (b) a sequence involving dissolving metal reduction of cyclazocine methyl ether, followed by oximination and Semmler--Wolff rearrangement. Several analogues were prepared and tested.
Subject(s)
Cyclazocine/analogs & derivatives , Analgesics/chemical synthesis , Animals , Dose-Response Relationship, Drug , Mice , Narcotic Antagonists/chemical synthesis , Rats , Reaction Time/drug effects , Structure-Activity Relationship , Time FactorsABSTRACT
May's benzomorphan synthesis leads not only to the alpha or cis isomer and the beta or trans isomer but also to a position isomer hereinafter called the gamma isomer. The structure and synthesis of this isomer are described. Biological activities of the alpha and gamma isomers are compared.
Subject(s)
Benzomorphans , Morphinans , Animals , Benzomorphans/analogs & derivatives , Benzomorphans/pharmacology , Chemical Phenomena , Chemistry , Isomerism , Morphinans/analogs & derivatives , Morphinans/pharmacology , Narcotic Antagonists , Narcotics , Rats , Structure-Activity RelationshipABSTRACT
In a benzomorphan bearing an antagonist side chain, introduction on the methano bridge of a hydroxyl oriented away from nitrogen has little effect on antagonist activity whereas a hydroxyl oriented toward nitrogen enhances this activity. Hydroxylation tends to decrease analgesic activity.
