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

doi:10.3109/14756366.2015.1010530

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

Centro di Riferimento Oncologico

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	137-146
Number of pages	10
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	31
Issue number	1
DOIs	https://doi.org/10.3109/14756366.2015.1010530
Publication status	Published - Jan 2 2016

Keywords

Hydrolase
MAGL
MAGL inhibitors
monoacylglycerol lipase
monoacylglycerol lipase inhibitors

ASJC Scopus subject areas

Drug Discovery
Pharmacology

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10.3109/14756366.2015.1010530

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title = "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.",

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

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T1 - 4-Aryliden-2-methyloxazol-5(4H)-one as a new scaffold for selective reversible MAGL inhibitors

AU - Granchi, Carlotta

AU - Rizzolio, Flavio

AU - Bordoni, Vittorio

AU - Caligiuri, Isabella

AU - Manera, Clementina

AU - Macchia, Marco

AU - Minutolo, Filippo

AU - Martinelli, Adriano

AU - Giordano, Antonio

AU - Tuccinardi, Tiziano

PY - 2016/1/2

Y1 - 2016/1/2

N2 - 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.

AB - 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.

KW - Hydrolase

KW - MAGL

KW - MAGL inhibitors

KW - monoacylglycerol lipase

KW - monoacylglycerol lipase inhibitors

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JO - Journal of Enzyme Inhibition and Medicinal Chemistry

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

Abstract

Keywords

ASJC Scopus subject areas

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