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.

@article{Kato2014DiscoveryO1,
  title={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.},
  author={Yuko Kato and Nobuhiro Fuchi and Yutaka Nishimura and Ayano Watanabe and Mai Yagi and Yasuhito Nakadera and Eriko Higashi and Masateru Yamada and Takumi Aoki and Hideo Kigoshi},
  journal={Bioorganic & medicinal chemistry letters},
  year={2014},
  volume={24 2},
  pages={
          565-70
        }
}
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… CONTINUE READING

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