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Stereochemical influences upon the opioid ligand activities of 4‐alkyl‐4‐arylpiperidine derivatives
Author(s) -
Casy A. F.,
Dewar G. H.,
Al Deeb Omar A.A.
Publication year - 1989
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530010305
Subject(s) - chemistry , stereochemistry , aryl , alkyl , ligand (biochemistry) , protonation , antagonist , in vivo , receptor , organic chemistry , biochemistry , ion , microbiology and biotechnology , biology
The synthesis and stereochemistry (configuration and preferred solute conformation) of some 4‐alkyl (methyl, n ‐propyl, isobutyl)‐4‐(3‐hydrxyphenyl)‐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.