Stereochemical influences upon the opioid ligand activities of 4-alkyl-4-arylpiperidine derivatives.
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.
Casy
A F
AF
School of Pharmacy and Pharmacology, University of Bath, England.
Dewar
G H
GH
al Deeb
O A
OA
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D008024:Ligands; D051379:Mice; D008968:Molecular Conformation; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects*
D008024:Ligands; D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid