Aromatic esters of nonquaternary carbon-4 piperidinols as analgesics
- 1 July 1978
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 21 (7) , 628-633
- https://doi.org/10.1021/jm00205a007
Abstract
Aromatic carboxylic esters of 1-methyl-4-piperidinol were prepared and evaluated for analgesic activity. Aralkyl, alkyl and cycloalkyl carboxylates of the 4-piperidinol system and 3,4-dimethoxybenzoates of isomeric piperidinols (24-26) were synthesized. The 3,4-dimethoxybenzoate 23 was nearly twice as active as codeine in the mouse hot-plate assay. In monkeys, 23 showed no morphine-like physical dependence liability. Cis- and trans-1,3-dimethyl-4-piperidinol esters 24 and 25 showed no binding to the opiate receptor in rat brain homogenates. The 3- and 4-monosubstituted and the 3,4-disubstituted benzoate esters were examined for qualitative structure-activity relationships with respect to parameters Esc and .pi.. Various structural features of this series of compounds that may have an affinity for receptor binding sites are discussed.This publication has 10 references indexed in Scilit:
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