New FAAH inhibitors based on 3-carboxamido-5-aryl-isoxazole scaffold that protect against experimental colitis

Université Lille Nord de France, ICPAL, EA 4481, IFR114, 3 rue du Professeur Laguesse, BP-83, F-59006 Lille, France.
Bioorganic & medicinal chemistry (Impact Factor: 2.79). 06/2011; 19(12):3777-86. DOI: 10.1016/j.bmc.2011.04.057
Source: PubMed


Growing evidence suggests a role for the endocannabinoid (EC) system, in intestinal inflammation and compounds inhibiting anandamide degradation offer a promising therapeutic option for the treatment of inflammatory bowel diseases. In this paper, we report the first series of carboxamides derivatives possessing FAAH inhibitory activities. Among them, compound 39 displayed significant inhibitory FAAH activity (IC(50) = 0.088 mu M) and reduced colitis induced by intrarectal administration of TNBS.

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Available from: Madjid Djouina, Aug 05, 2014
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    • "This is seen in the conclusions to many studies incorporating such models, or indeed articles reviewing the use of these models, which tend to finish with statements referring to future, rather than current, therapeutic advances. Some examples of such conclusions are as follows (note that italics are not in the original references): " ...promising target for the Inflammatory Bowel Diseases (IBD) treatment " (Andrzejak et al., 2011); " substantial investment from the pharmaceutical industry should deliver novel therapies arising from gene discovery to the clinic within the next 5 years " (Lees et al., 2011); " ...recently established genetically engineered mouse models lacking IBD susceptibility gene should be promising tools to develop novel therapeutic measures for IBD " (Mizoguchi and Mizoguchi, 2010). This is not to detract from some excellent research in the field, and the recently established genetically engineered mouse models lacking IBD susceptibility genes should indeed prove to be promising tools to develop novel therapies. "

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