Stereochemical influences upon the opioid ligand activities of 4-alkyl-4-arylpiperidine derivatives |
| |
Authors: | A F Casy G H Dewar O A al Deeb |
| |
Institution: | School of Pharmacy and Pharmacology, University of Bath, England. |
| |
Abstract: | The synthesis and stereochemistry (configuration and preferred solute conformation) of some 4-alkyl (methyl, n-propyl, isobutyl)-4-(3-hydroxy-phenyl)-1-methylpiperidines and corresponding 3-methyl diastereoisomeric pairs are reported, together with their in vivo and in vitro activities as opioid ligands. All potent agonists exhibit a preference for axial 4-aryl chair conformations when protonated, and stereochemical analogies with rigid opioids of the benzomorphan class are discussed. Antagonist properties are found in compounds with preference for equatorial 4-aryl chairs, notably the cis 3,4-dimethyl derivative. |
| |
Keywords: | opioid ligand 4-arylpiperidines conformation NMR |
|
|