Azabicycloalkanes as Analgetics. I. Synthesis of 1-Phenyl-6-azabicyclo [3, 2, 1] octane Derivatives

Abstract

As part of studies on azabicycloalkanes as analgetics with narcotic antagonist activity, 1-phenyl-6-azabicyclo [3, 2, 1] octane derivatives have been synthesized. Bromination of the keto amide (IXa, b) followed by treatment with sodium methoxide gave the bicyclic keto lactam (XIa, b) respectively. A number of drivatives bearing various substituents on nitrogen and C₇ have been prepared from (XIa, b) for pharmacological evaluation. 6, 7-endo-Dimethyl-1-(3-hydroxyphenyl)-6-azabicyclo [3, 2, 1] octane (XXc) and its dextro isomers exhibited analgetic activities on the order of meperidine and morphine, respectively. They also had narcotic antagonist activity with a low grade of abuse potential.