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

Carlotta Granchi, Flavio Rizzolio, Vittorio Bordoni, Isabella Caligiuri, Clementina Manera, Marco Macchia, Filippo Minutolo, Adriano Martinelli, Antonio Giordano, Tiziano Tuccinardi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2 2016

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

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    Granchi, C., Rizzolio, F., Bordoni, V., Caligiuri, I., Manera, C., Macchia, M., Minutolo, F., Martinelli, A., Giordano, A., & Tuccinardi, T. (2016). 4-Aryliden-2-methyloxazol-5(4H)-one as a new scaffold for selective reversible MAGL inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(1), 137-146. https://doi.org/10.3109/14756366.2015.1010530