Optical isomers of some piperidine-derived hemicholinium congeners containing secondary alcohol groups: preparation and biological activities.
Previous publications on the title compounds, 1 and 2 ('A-4' and 'A-5'), reported pharmacological data on what were probably mixtures of optical isomers of unknown composition. The compounds can exist as an enantiomeric pair as well as a diastereomeric meso isomer. In the present work, all possible stereoisomers (meso and dextrorotatory and levorotatory isomers) of the piperidine derivatives 'A-4' and 'A-5' have been isolated, identified, and characterized, and pharmacological data have been obtained on all products. In all of the bioassays conducted, optical isomers of each structure exhibited similar qualitative and quantitative effects. We conclude that the stereochemical nature of the chiral centers bearing secondary alcohol groups in these molecules does not play a critical role in interactions with in vivo receptors, and therefore that the alcohol groups in 'A-4' and 'A-5' are not prime sites of interaction(s) with receptor(s).
Cannon
J G
JG
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
Wang
Y F
YF
Sheff
K
K
Tedford
C E
CE
Chatterjee
T
T
Bhatnagar
R
R
Long
J P
JP
D000438:Alcohols / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002794:Choline / Q000378:metabolism; D006426:Hemicholinium 3 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000438:Alcohols; D010880:Piperidines; D006426:Hemicholinium 3; D002794:Choline