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Bioorg Med Chem Lett. 2012 Sep 15;22(18):5889-92. doi: 10.1016/j.bmcl.2012.07.074. Epub 2012 Aug 2.

Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase.

Author information

1
Department of Entomology and UC Davis Comprehensive Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, USA.

Abstract

Substituted ureas with a carboxylic acid ester as a secondary pharmacophore are potent soluble epoxide hydrolase (sEH) inhibitors. Although the ester substituent imparts better physical properties, such compounds are quickly metabolized to the corresponding less potent acids. Toward producing biologically active ester compounds, a series of esters were prepared and evaluated for potency on the human enzyme, stability in human liver microsomes, and physical properties. Modifications around the ester function enhanced in vitro metabolic stability of the ester inhibitors up to 32-fold without a decrease in inhibition potency. Further, several compounds had improved physical properties.

PMID:
22901393
PMCID:
PMC3432147
DOI:
10.1016/j.bmcl.2012.07.074
[Indexed for MEDLINE]
Free PMC Article

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