Design, synthesis and biological evaluation of novel α-aminoamide derivatives / 国际药学研究杂志

ABSTRACT

Objective: To design and synthesize novel α-aminoamide derivatives for the treatment of neuropathic pain. Methods: Ralfinamide was used as a lead compound, and it's ring A was replaced by a benzoheterocyclic moiety(2, 3-dihydrobenzofuran or 2, 3-dihydrobenzo[b][1, 4]dioxin)to obtain the new compounds 5a-5f. The in vivo and in vitro analgesic activities of the new compounds were evaluated by the formalin test and the whole-cell patch clamp assay, respectively. Results: In the formalin test in vivo, compound 5e exhibited higher analgesic activities(60% higher)than ralfinamide(P<0.05). The whole-cell patch clamp assay showed that the inhibitory effect of all tested compounds, except for 5d, on sodium channel Nav1.7 was much weaker than ralfinamide (P<0.05 or P<0.01). Conclusion: A set of new compounds with better analgesic activities than ralfinamide were obtained via optimizing the structure of ring A of ralfinamide. The reults of this study can provide useful references for relative research.