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Discovery of 1-oxa-4,9-diazaspiro[5.5]undecane-based trisubstituted urea derivatives as highly potent soluble epoxide hydrolase inhibitors and orally active drug candidates for treating of chronic kidney diseases.
Kato, Yuko; Fuchi, Nobuhiro; Nishimura, Yutaka; Watanabe, Ayano; Yagi, Mai; Nakadera, Yasuhito; Higashi, Eriko; Yamada, Masateru; Aoki, Takumi; Kigoshi, Hideo.
Afiliación
  • Kato Y; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan; Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan. Electronic address: Yuko_Kato@nts.toray.co.
  • Fuchi N; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Nishimura Y; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Watanabe A; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Yagi M; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Nakadera Y; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Higashi E; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Yamada M; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Aoki T; Toray Industries, Inc., Pharmaceutical Research Laboratories, 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
  • Kigoshi H; Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan.
Bioorg Med Chem Lett ; 24(2): 565-70, 2014 Jan 15.
Article en En | MEDLINE | ID: mdl-24373724
We identified 1-oxa-4,9-diazaspiro[5.5]undecane-based trisubstituted ureas as highly potent soluble epoxide hydrolase (sEH) inhibitors and orally active agents for treating chronic kidney diseases. Compound 19 exhibited excellent sEH inhibitory activity and bioavailability. When administered orally at 30 mg/kg, 19 lowered serum creatinine in a rat model of anti-glomerular basement membrane glomerulonephritis but 2,8-diazaspiro[4.5]decane-based trisubstituted ureas did not. These results suggest that 19 is an orally active drug candidate for treating chronic kidney diseases.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Urea / Alcanos / Epóxido Hidrolasas / Insuficiencia Renal Crónica / Descubrimiento de Drogas Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2014 Tipo del documento: Article
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Urea / Alcanos / Epóxido Hidrolasas / Insuficiencia Renal Crónica / Descubrimiento de Drogas Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2014 Tipo del documento: Article