Design, synthesis, and biological evaluation of acyl sulfonamide derivatives with spiro cycles as NaV1.7 inhibitors for antinociception
作者:Xiangshuo Ouyang、Min Su、Dengqi Xue、Liying Dong、Heling Niu、Wei Li、Yani Liu、KeWei Wang、Liming Shao
DOI:10.1016/j.bmc.2023.117290
日期:2023.5
voltage-gated sodium channel NaV1.7 preferentially expressed in sensory neurons of dorsal root ganglia (DRG) serves a promising target for pain therapy. Here, we report the design, synthesis, and evaluation of a series of acyl sulfonamide derivatives targeting Nav1.7 for their antinociceptive activities. Among the derivatives tested, the compound 36c was identified as a selective and potent NaV1.7 inhibitor
慢性疼痛作为未满足的医疗需求,严重影响生活质量。优先在背根神经节 (DRG)的感觉神经元中表达的电压门控钠通道 Na V 1.7 为疼痛治疗提供了一个有前途的目标。在这里,我们报告了一系列针对 Nav1.7 的酰基磺酰胺衍生物的抗伤害活性的设计、合成和评估。在所测试的衍生物中,化合物36c在体外被鉴定为一种选择性且有效的 Na V 1.7 抑制剂,并在体内表现出镇痛作用。36c的鉴定不仅为选择性Na的发现提供了新的思路V 1.7 抑制剂,但也可能为疼痛治疗提供前提。