4-Aryliden-2-methyloxazol-5(4H)-one as a new scaffold for selective reversible MAGL inhibitors. (2nd January 2016)

• Record Type: Journal Article
• Authors: Granchi, Carlotta; Rizzolio, Flavio; Bordoni, Vittorio; Caligiuri, Isabella; Manera, Clementina; Macchia, Marco; Minutolo, Filippo; Martinelli, Adriano; Giordano, Antonio; Tuccinardi, Tiziano
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 1(2016:Feb.)
• Page Start: 137
• Page End: 146
• Publication Date: 2016-01-02
• Subjects: Hydrolase -- MAGL -- MAGL inhibitors -- monoacylglycerol lipase -- monoacylglycerol lipase inhibitors; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2015.1010530
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: This study reports on a preliminary structure–activity relationship exploration of 4-aryliden-2-methyloxazol-5(4 H )-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 compound16b (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.