Identification of 2-(2'-fluoro-[1,1'-biphenyl]-2-yl)acetamide as a Sodium Valproate-like broad spectrum anti-epileptic drug candidate.


Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 3-1-98 Kasugade-naka Konohana-ku, Osaka 554-0022, Japan. Electronic address: [Email]


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.


1,1′-Biphenyl-2-acetamide,Epilepsy,In vivo screening,MES,PTZ,