Screening of 100 acylsulfonamides from the Bristol-Myers Squibb compound collection identified the C3-cyclohexyl indole 6 as a potent Nav1.7 inhibitor. Replacement of the C2 furanyl ring of 6 with a heteroaryl moiety or truncation of this group led to the identification of 4 analogs with hNav1.7 IC50 values under 50 nM. Fluorine substitution of the truncated compound 12 led to 34 with improved potency and isoform selectivity. The inverted indole 36 also maintained good activity. Both 34 and 36 exhibited favorable CYP inhibition profiles, good membrane permeability and a low efflux ratio and, therefore, represent new leads in the search for potent and selective Nav1.7 inhibitors to treat pain.

中文翻译：

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发现新的基于吲哚的酰基磺酰胺Nav1.7抑制剂。

从百时美施贵宝公司的化合物中筛选出100种酰基磺酰胺，确定C3-环己基吲哚6是有效的Nav1.7抑制剂。用杂芳基部分取代6的C2呋喃基环或该基团的截短可鉴定出hNav1.7 IC50值低于50 nM的4个类似物。截短的化合物12的氟取代导致34具有改进的效力和同工型选择性。倒立的吲哚36也保持良好的活性。34和36均表现出良好的CYP抑制特性，良好的膜通透性和较低的流出比，因此，代表了寻找有效和选择性的Nav1.7抑制剂来治疗疼痛的新途径。