Discovery libraries targeting the major enzyme classes: The serine hydrolases

作者：Otrubova Katerina; Srinivasan Venkat; Boger Dale L^*

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(16): 3807-3813.

DOI：10.1016/j.bmcl.2014.06.063

• Serine hydrolase inhibitors
• Enzyme inhibitors
• Screening library
• Fatty acid amide hydrolase

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 K-i = 100-200 pM) complementary to those previously disclosed enlisting electron-deficient aniline-based ureas.

• 出版日期2014-8-15