2. Academic Validation
  3. 4-Aryliden-2-methyloxazol-5(4H)-one as a new scaffold for selective reversible MAGL inhibitors

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

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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