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

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

  • Bioorg Med Chem Lett. 2019 Jan 15;29(2):138-142. doi: 10.1016/j.bmcl.2018.12.014.
Tomoyuki Tanaka 1,  Nana Yajima 2,  Tomoko Kiyoshi 2,  Yoshiki Miura 2,  Yoshifumi Inoue 2,  Takuya Nishimaki 2,  Seiji Iwama 2
Affiliations

Affiliations

  • 1 Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 3-1-98 Kasugade-naka Konohana-ku, Osaka 554-0022, Japan. Electronic address: [email protected].
  • 2 Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 3-1-98 Kasugade-naka Konohana-ku, Osaka 554-0022, Japan.
PMID: 30551904 DOI: 10.1016/j.bmcl.2018.12.014
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.

Keywords

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

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