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Discovery libraries targeting the major enzyme classes: the serine hydrolases.

ABSTRACT: Two libraries of modestly reactive ureas containing either electron-deficient acyl anilines or acyl pyrazoles were prepared and are reported as screening libraries for candidate serine hydrolase inhibitors. Within each library is a small but powerful subset of compounds that serve as a chemotype fragment screening library capable of subsequent structural diversification. Elaboration of the pyrazole-based ureas provided remarkably potent irreversible inhibitors of fatty acid amide hydrolase (FAAH, apparent Ki=100-200 pM) complementary to those previously disclosed enlisting electron-deficient aniline-based ureas.

SUBMITTER: Otrubova K

PROVIDER: S-EPMC4130767 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Discovery libraries targeting the major enzyme classes: the serine hydrolases.

Otrubova Katerina K Srinivasan Venkat V Boger Dale L DL

Bioorganic & medicinal chemistry letters 20140627 16

Two libraries of modestly reactive ureas containing either electron-deficient acyl anilines or acyl pyrazoles were prepared and are reported as screening libraries for candidate serine hydrolase inhibitors. Within each library is a small but powerful subset of compounds that serve as a chemotype fragment screening library capable of subsequent structural diversification. Elaboration of the pyrazole-based ureas provided remarkably potent irreversible inhibitors of fatty acid amide hydrolase (FAAH ...[more]

PMID: 25037918

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