4-Aryliden-2-methyloxazol-5(4H)-one as a new scaffold for selective reversible MAGL inhibitors

Abstract

This study reports on a preliminary structure–activity relationship exploration of 4-aryliden-2-methyloxazol-5(4H)-one-based compounds as MAGL/FAAH inhibitors. Our results highlight that this scaffold may serve for the development of selective MAGL inhibitors. A 69-fold selectivity against MAGL over FAAH was achieved for compound 16b (MAGL and FAAH IC₅₀ = 1.6 and 111 µM, respectively). Furthermore, the best compound behaved as a reversible ligand and showed promising antiproliferative activity in cancer cells.

• Hydrolase
• MAGL
• MAGL inhibitors
• monoacylglycerol lipase
• monoacylglycerol lipase inhibitors

Declaration of interest

Financial support for this project was provided by the Italian Ministero dell’Università e della Ricerca (MIUR), under the National Interest Research Projects framework (PRIN_2010_5YY2HL). The authors report no declarations of interest