Synthesis, pharmacological action, and receptor binding affinity of the enantiomeric 1-(1-phenyl-3-methylcyclohexyl)piperidines.
The cis and trans enantiomers of the 1-(1-methylcyclohexyl)piperidines were prepared from either 3(R)- or 3(S)-methylcyclohexanone through the Bruylents reaction or a modified azide route, respectively. Separation of the intermediate amines 5 and 6 was achieved through chromatography or selective crystallization of a fumarate salt. The cis isomer 2b had about one-third of the affinity of phencyclidine for the PCP receptor. The other isomers were less potent. There was a 40-fold difference between the binding affinity of the cis enantiomers 2a and 2b and a fourfold difference between the affinities of the trans enantiomers 1a and 1b. None of the compounds antagonized the stereotypy induced by phencyclidine in the rotorod assay in mice, after intraperitoneal introduction.
Thurkauf
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A
Section on Drug Design and Synthesis, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Hillery
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P
Mattson
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MV
Jacobson
A E
AE
Rice
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KC
D000818:Animals; D001667:Binding, Competitive; D066298:In Vitro Techniques; D051379:Mice; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D017478:Receptors, Phencyclidine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D010880:Piperidines; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D010622:Phencyclidine