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Search for monoglyceride lipase inhibitors: synthesis and screening of arylthioamides derivatives

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Abstract

Monoglyceride lipase (MGL) is the enzyme responsible for the termination of 2-arachidonoylglycerol (2-AG) signalling, an endogenous ligand for the G-protein coupled cannabinoid receptors CB1 and CB2. Its known abundance and physiological roles emphasize the interest of MGL as an attractive therapeutic target. Search for MGL inhibitors was undertaken by screening an arylthioamide series. The evaluation of arylthioamides derivatives activity as MGL inhibitors measured by the hydrolysis of [3H]-2-oleoylglycerol by human purified MGL led to the identification of (2-chloro-phenyl)-morpholin-4-yl-methanethione (2) and (3-nitro-phenyl) morpholin-4-yl-methanethione (12), which moreover exhibit good selectivity compared with human fatty acid amide hydrolase inhibition.

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Acknowledgements

This work was supported by a research grant from the FNRS (FRSM 3.4.625.07 and FRFC 2.4.654.06) and C.N.K. is very indebted to the “Coopération technique belge” and the” Fonds Spécial de Recherche” (Université catholique de Louvain) for their respective fellowships.

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Authors and Affiliations

  1. Drug Design and Discovery Center, Unité de Chimie Pharmaceutique et de Radiopharmacie, Département des Sciences Pharmaceutiques, Faculté de Médecine, Université Catholique de Louvain, Avenue E. Mounier 73-40, 1200, Bruxelles, Belgium

    Coco N. Kapanda, Giulio G. Muccioli, Geoffray Labar, Nihed Draoui, Didier M. Lambert & Jacques H. Poupaert

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  1. Coco N. Kapanda
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  2. Giulio G. Muccioli
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  3. Geoffray Labar
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  4. Nihed Draoui
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  5. Didier M. Lambert
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  6. Jacques H. Poupaert
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Correspondence to Jacques H. Poupaert.

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Kapanda, C.N., Muccioli, G.G., Labar, G. et al. Search for monoglyceride lipase inhibitors: synthesis and screening of arylthioamides derivatives. Med Chem Res 18, 243–254 (2009). https://doi.org/10.1007/s00044-008-9123-2

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  • DOI: https://doi.org/10.1007/s00044-008-9123-2

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