[Design, synthesis and antalgic activities of aralkyl-ketone-4-piperidol derivatives].
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.
Wang
Guan
G
Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
Zhang
Gui-sen
GS
Guo
Lin
L
Chen
Jie
J
Li
Jian-qi
JQ
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D051379:Mice; D015394:Molecular Structure; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013329:Structure-Activity Relationship
D018712:Analgesics, Non-Narcotic; D010881:Piperidones; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu