By further optimizing compound A [2'-fluoro-N-methyl-[1,1'-biphenyl]-2-sulfonamide], we identified DSP-0565 [2-(2'-fluoro-[1,1'-biphenyl]-2-yl)acetamide, 17a] as a strong, broad-spectrum anti-epileptic drug (AED) candidate. Our efforts mainly focused on finding an alternative polar group for the sulfonamide in order to improve ADME profile of compound A including good metabolic stability and no reactive metabolic production. This led to the identification of biphenyl acetamide as a new scaffold for development of broad-spectrum AED candidates. DSP-0565 showed anti-convulsant activity in various models (scPTZ, MES, 6 Hz and amygdala kindling) with good safety margin, and was therefore selected as a clinical candidate.

中文翻译：

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鉴定2-（2'-氟-[1,1'-联苯] -2-基）乙酰胺为丙戊酸钠样广谱抗癫痫药候选物。

通过进一步优化化合物A [2'-氟-N-甲基-[1,1'-联苯] -2-磺酰胺]，我们确定了DSP-0565 [2-（2'-氟-[1,1'-联苯] ] -2-基）乙酰胺（17a]是一种强大的广谱抗癫痫药（AED）候选物。我们的努力主要集中在寻找磺酰胺的替代极性基团，以改善化合物A的ADME谱，包括良好的代谢稳定性和无反应性代谢产物。这导致联苯乙酰胺被鉴定为开发广谱AED候选物的新支架。DSP-0565在各种模型（scPTZ，MES，6 Hz和杏仁核点燃）中显示出抗惊厥活性，并具有良好的安全裕度，因此被选为临床候选药物。