Stereochemical studies of the 4‐alkyl‐4‐arylpiperidine class of opioid ligand

Abstract

Abstract The 1 H (270, 400 MHz) and 13 C (67.5 MHz) NMR spectra of some 4‐methyl‐ (also 4‐ n ‐propyl‐ and ‐isobutyl)‐4‐(3‐hydroxy‐ and 3‐methoxy‐phenyl)piperidines and their 3‐methyl diastereoisomers are reported. Many of the compounds had opioid ligand activities. The data were analysed in terms of preferred conformation and configuration (3‐methyl derivatives). Only compounds with preference for axial 4‐aryl chair conformations displayed marked agonist properties and the one potent antagonist, cis ‐1,3,4‐trimethyl‐4‐(3‐hydroxyphenyl)piperidine, favoured an equatorial 4‐aryl chair.