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.