Azabicycloalkanes as analgetics. VI. 5-Phenyl-2-azabicyclo[3,2,1]octanes.

Abstract

As part of a study on the structure-activity relationships of the partial agonist activity of phenylazabicycloalkane analgetics, the title compound (I), a 5 membered alicyclic analog of a known analgetic agent, was synthesized. The aminoketone was converted to I via the 8-oxo derivative by the usual method. Alternatively, intramolecular Michael reaction of the amino cyclopentenone derivative generated in situ by hydrolysis of the urethane gave the 6-oxo derivative (XII) convertible also to I. Finally and most conveniently, the keto enamines obtained by mercuric acetate oxidation of 2 compounds were cyclized to XII and another compound by heating them with aqueous acetic acid. I was analgetically inactive [in mice] but exhibited narcotic antagonist activity [to morphine-induced respiratory depression in the rabbit] comparable to pentazocine. Certain structural correlations between I and other phenylazabicycloalkane analgetics are discussed.