- Discovery libraries targeting the major enzyme classes: the serine hydrolases.
Discovery libraries targeting the major enzyme classes: the serine hydrolases.
Bioorganic & medicinal chemistry letters (2014-07-20)
Katerina Otrubova, Venkat Srinivasan, Dale L Boger
PMID25037918
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.
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