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

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.

SUBMITTER: Kim IH

PROVIDER: S-EPMC3432147 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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

Kim In-Hae IH Nishi Kosuke K Kasagami Takeo T Morisseau Christophe C Liu Jun-Yan JY Tsai Hsing-Ju HJ Hammock Bruce D BD

Bioorganic & medicinal chemistry letters 20120802 18

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 es ...[more]

PMID: 22901393

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