Med Chem Res (2009) 18:243–254
Search for monoglyceride lipase inhibitors: synthesis and screening of arylthioamides derivatives

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

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.