Stereochemical studies on medicinal agents. 25. Absolute configuration and analgetic potency of beta-1,2-dimethyl-2-phenyl-4-(propionyloxy)piperidine enantiomers.

Abstract

Enantiomers of beta-1,2-dimethyl-4-phenyl-4-(propionyloxy)piperidine (4) were employed as probes to demonstrate that opioid receptors are capable of distinguishing between the enantiotopic edges (the Ogston effect) of the piperidine ring. These enantiomers, (-)- and (+)-4.HCl, were prepared by esterification of the corresponding alcohols, (+)- and (-)-4a. Single crystal X-ray studies of (-)-4a.HCl reveal that it possesses the 2R,4S absolute configuration. Analgetic testing in mice (hot-plate) and receptor binding studies indicate that (-)-(2S,4R)-4.HCl is approximately ten times more potent than its enantiomer. The results are consistent with the operation of the Ogston effect in the interaction of achiral 4-phenylpiperidines with opioid receptors. Additionally, it is suggested that the piperidine ring of these and other closely related 4-phenylpiperidines bind within a receptor subsite cleft whose dimensions exclude diequatorial 2,6- and 3,5-dimethyl-substituted ligands.

Cite this paper

@article{Fries1982StereochemicalSO, title={Stereochemical studies on medicinal agents. 25. Absolute configuration and analgetic potency of beta-1,2-dimethyl-2-phenyl-4-(propionyloxy)piperidine enantiomers.}, author={Dietrich Fries and Randy Dodge and H{\aa}kon Hope and Philip S. Portoghese}, journal={Journal of medicinal chemistry}, year={1982}, volume={25 1}, pages={9-12} }