摘要
Small molecule sodium ion channel blockers with a pharmacophore of a-aminoamide have exhibited anti-allodynia effects on neuropathic pain. A library of new a-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, Navl.7, in a whole-cell patch clamp assay. These results suggest that introduction of the moiety of substituted benzene to a-aminoamide derivatives can improve their bioactivity and further study is warranted.
Small molecule sodium ion channel blockers with a pharmacophore of a-aminoamide have exhibited anti-allodynia effects on neuropathic pain. A library of new a-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, Navl.7, in a whole-cell patch clamp assay. These results suggest that introduction of the moiety of substituted benzene to a-aminoamide derivatives can improve their bioactivity and further study is warranted.
基金
the Beijing Municipal Science and Technology Project(No.Z131100002713004)
National Science and Technology Major Project of China(No.2012ZX09301003)
