1977 Volume 25 Issue 4 Pages 775-783
As part of a study on the steric aspects of the partial agonist activity of phenylazabicycloalkane analgetics, the title compound (A), a skeletal isomer of the known partial agonist (I), was synthesized. The keto ester (IV) was converted to the lactam (VIII) either by hydrogenation of the oxime (V) or by reductive amination. VIII gave A bearing various substituents. Alternatively, A was obtained from the unsaturated amine (XVI) via the bridged aziridine (XVII). Generally, no discernible analgetic activity was observed for A. However, the two N-methyl compounds (Xf and XIc) exhibited narcotic antagonist activity on the order of I and pentazocine. The simple N-methyl-3-phenylpiperidines (II), a prototype of both I and A, also showed comparable antagonist activity. These results support the idea that the N-methylphenethylamine fragment in I is responsible for its antagonist activity. Replacement of the N-methyl group of Xf by an allyl and a propyl group conferred increased antagonist activity. This shift of the potency parallels that observed for II previously.