Synthesis and evaluation of novel α-aminoamides with substituted benzene scaffold for the treatment of neuropathic pain

Abstract Small molecule sodium ion channel blockers with a pharmacophore of α -aminoamide have exhibited anti-allodynia effects on neuropathic pain. A library of new α -aminoamide derivatives containing a scaffold of substituted benzene were designed and synthesized. These compounds were evaluated in mice formalin model and they exhibited significant analgesic activities. However, the anti-allodynia mechanism of these compounds remains unclear; some of the target compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. These results suggest that introduction of the moiety of substituted benzene to α -aminoamide derivatives can improve their bioactivity and further study is warranted.