Probes for Narcotic Receptor Mediated Phenomena. 39. Enantiomeric N-Substituted Benzofuro23-cpyridin-6-ols: Synthesis and Topological Relationship to Oxide-bridged Phenylmorphans

摘要

Enantiomers of N-substituted benzofuro[2,3-c]pyridin-6-ols have been synthesized and the subnanomolar affinity and potent agonist activity of the known racemic N-phenethyl substituted benzofuro[2,3-c]pyridin-6-ol can now be ascribed to the 4aS,9aR enantiomer. The energy minimized structures suggest that the active enantiomer bears a greater three-dimensional resemblance to morphine than to an ostensibly structurally similar oxide-bridged phenylmorphan. Structural features of the conformers of N-substituted benzofuro[2,3-c]pyridin-6-ols were compared to provide the rationale for their binding affinity.