Design, synthesis and antalgic activities of aralkyl-ketone-4-piperidol derivatives.
- Author:
Guan WANG
1
;
Gui-sen ZHANG
;
Lin GUO
;
Jie CHEN
;
Jian-qi LI
Author Information
1. Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
- Publication Type:Journal Article
- MeSH:
Analgesics, Non-Narcotic;
chemical synthesis;
chemistry;
pharmacology;
Animals;
Mice;
Molecular Structure;
Pain Measurement;
Pain Threshold;
drug effects;
Piperidones;
chemical synthesis;
chemistry;
pharmacology;
Receptors, Opioid, delta;
metabolism;
Receptors, Opioid, kappa;
metabolism;
Receptors, Opioid, mu;
metabolism;
Structure-Activity Relationship
- From:
Acta Pharmaceutica Sinica
2009;44(4):371-378
- CountryChina
- Language:Chinese
-
Abstract:
A series of aralkyl-ketone-4-piperidol derivatives were synthesized and tested for their analgesic activities. All of the novel 30 compounds were prepared from 4-piperidone and alpha-halo-aralkyl-ketone through five steps, including Boc protection, nucleophilic addition in presence of CeCl3/NaI catalyst, deprotection, condensation and salification. Their structures were confirmed by 1H NMR and HRMS. Preliminary in vivo pharmacological trials showed that most of the synthesized compounds revealed analgesic effects. Among the tested compounds, 8, 13 and 22 exhibited potent analgesic activities in both mice writhing and mice hot plate model. The three compounds have low affinity for mu, delta, kappa receptors, which is a chance to find a better precursor of non-opioid analgesic for further optimization.
