Synthesis and Evaluation of Novel α-Aminoamides Containing Benzoheterocyclic Moiety for the Treatment of Pain

Novel alpha-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Na(v)1.7 and anti-Na(v)1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Na-v targets, could serve as new leads for the development of analgesic medicines.

Automated summary

Novel alpha-aminoamide derivatives containing different benzoheterocyclic moieties were synthesized and evaluated for their potential as voltage-gated sodium ion channel blockers for pain treatment. Compounds 6a, 6e, and 6f displayed stronger in vivo analgesic activity than ralfinamide and also showed potent in vitro anti-Na(v)1.7 and anti-Na(v)1.8 activity, suggesting their potential as new leads for the development of analgesic drugs targeting pain-related Na-v channels.