4-Amino-4-arylcyclohexanones and their derivatives: a novel class of analgesics. 2. Modification of the carbonyl function

The effect on potency of modification of the carbonyl function of analgesics derived from 4-(dimethylamino)-4-arylcyclohexan-1-one was studied by reduction and by addition of nucleophiles. The resulting amino alcohols were separated and assigned structures on the basis of X-ray crystallography, NMR,...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1981-04, Vol.24 (4), p.404-408
Main Authors: Lednicer, Daniel, VonVoigtlander, Philip F, Emmert, D. Edward
Format: Article
Language:English
Subjects:
Analgesics - chemical synthesis
Analgesics - pharmacology
Animals
Cyclohexanes - chemical synthesis
Cyclohexanones - chemical synthesis
Cyclohexanones - pharmacology
Female
Mice
Structure-Activity Relationship
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Summary:The effect on potency of modification of the carbonyl function of analgesics derived from 4-(dimethylamino)-4-arylcyclohexan-1-one was studied by reduction and by addition of nucleophiles. The resulting amino alcohols were separated and assigned structures on the basis of X-ray crystallography, NMR, and TLC mobility. The trans (OH and N) isomers were invariably more potent than the cis. Inclusion of flat lipophilic moieties (phenyl, cyclohexenyl) at a distance of at least two carbon atoms from the carbon bearing hydroxyl led to increases in potency by orders of magnitude. The possible significance of this on receptor interaction is discussed.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00136a010