Identification of 2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide as a Sodium Valproate-like broad spectrum anti-epileptic drug candidate |
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Authors: | Tomoyuki Tanaka Nana Yajima Tomoko Kiyoshi Yoshiki Miura Yoshifumi Inoue Takuya Nishimaki Seiji Iwama |
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Institution: | Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 3-1-98 Kasugade-naka Konohana-ku, Osaka 554-0022, Japan |
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Abstract: | 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. |
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Keywords: | 1 1′-Biphenyl-2-acetamide Epilepsy MES PTZ |
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