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

  • J Enzyme Inhib Med Chem. 2016;31(1):137-46. doi: 10.3109/14756366.2015.1010530.
Carlotta Granchi  1 ,  Flavio Rizzolio  2 ,  Vittorio Bordoni  1 ,  Isabella Caligiuri  2 ,  Clementina Manera  1 ,  Marco Macchia  1 ,  Filippo Minutolo  1 ,  Adriano Martinelli  1 ,  Antonio Giordano  2 ,  Tiziano Tuccinardi  1  2
Affiliations
  • 1. a Department of Pharmacy , University of Pisa , Pisa , Italy and.
  • 2. b Sbarro Institute for Cancer Research and Molecular Medicine Center for Biotechnology, Temple University , Philadelphia , PA , USA.
PMID: 25669350 DOI: 10.3109/14756366.2015.1010530
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 IC(50) = 1.6 and 111 µM, respectively). Furthermore, the best compound behaved as a reversible ligand and showed promising antiproliferative activity in Cancer cells.

Keywords
Hydrolase; MAGL; MAGL inhibitors; monoacylglycerol lipase; monoacylglycerol lipase inhibitors.
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