Document Report Card

ID: ALA1122480

Journal: J Med Chem

Title: Synthesis and pharmacological studies of 4,4-disubstituted piperidines: a new class of compounds with potent analgesic properties.

Authors: Huegi BS, Ebnöther AM, Rissi E, Gadient F, Hauser D, Roemer D, Hill RC, Buescher HH, Petcher TJ.

Abstract: A series of 4,4-disubstituted piperidines has been synthesized and evaluated for analgesic activity. Several of these analogues show analgesic potency comparable to morphine in the mouse writhing and tail-flick tests. A number of compounds exhibit high affinity for [3H]naloxone binding sites in rat brain membranes. Among the most potent derivatives are compounds 15 and 48. Although opiate-like, attempts to modify this activity with various substituents have failed to produce antagonistic properties. A few of these analogues also show marked long-lasting serotonin antagonism in the guinea pig serotonin toxicity test and the DL-5-hydroxytryptophan induced head-twitch model in the mouse.

CiteXplore: 6600791

DOI: 10.1021/jm00355a010