Synthesis and preliminary biological evaluation of novel piperidine arylamide analgesic small molecules
OBJECTIVE To design and synthesize a series of novel small analgesic molecules and to preliminarily investigate their analgesic efficacy on chronic sciatic nerve constriction(CCI)in rats.METHODS Based on the structural modification of compound Ⅶ,a dual-target analgesic agent acting on σ1 and μ receptors,target products Ⅰ were synthesized from substituting different aromatic amines by the Wittig-Homer reaction,hydrogenation reduction reaction,carbonyl reduction reaction,and nucleophilic substitution reaction.A CCI rat model was establisted to analyze the analgesic properties of different compound structures.The mechanical pain thresholds of the rats were measured and compared before and after drug administration.RESULTS and CONCLUSION The three target compounds Ⅰ were synthesized,with their structures confirmed by NMR and ESI-MS.After-administration,the saline group showed no significant change in the mechanical pain threshold.In contrast,the experimental and positive control groups demonstrated an increase in the mechanical pain threshold of the rats.The analgesic effects of the experimental groups were not significantly different from those of the gabapentin group,indicating comparable efficacy.However,significant differences were observed when compared to the saline group,underscoring the potential of these compounds as effective analgesics.
NETL
NSTL
万方数据
