Design, synthesis and biological evaluation of potent FAAH inhibitors.
A new series of 3-carboxamido-5-aryl-isoxazoles was designed, synthesized and evaluated for their biological activity. Different pharmacomodulations have been explored and the lipophilicity of these compounds was assessed. Investigation of the in vitro biological activity led to the identification of 5 compounds as potent FAAH inhibitors, their good FAAH inhibition capacity is probably correlated with their suitable lipophilicity. Specifically, compound 25 showed similar inhibition potency against FAAH in comparison with URB597, one of the most potent FAAH inhibitor known to date.
ICPAL, Univ. Lille, Inserm, U995-LIRIC-Lille Inflammation Research International Center, 3 rue du Professeur Laguesse BP83, F-59006 Lille, France.
Wei
W
Tuo
ICPAL, Univ. Lille, Inserm, U995-LIRIC-Lille Inflammation Research International Center, 3 rue du Professeur Laguesse BP83, F-59006 Lille, France.
Natascha
N
Leleu-Chavain
ICPAL, Univ. Lille, Inserm, U995-LIRIC-Lille Inflammation Research International Center, 3 rue du Professeur Laguesse BP83, F-59006 Lille, France.
Amélie
A
Barczyk
ICPAL, Univ. Lille, Inserm, U995-LIRIC-Lille Inflammation Research International Center, 3 rue du Professeur Laguesse BP83, F-59006 Lille, France.
Nicolas
N
Renault
ICPAL, Univ. Lille, Inserm, U995-LIRIC-Lille Inflammation Research International Center, 3 rue du Professeur Laguesse BP83, F-59006 Lille, France.
Lucas
L
Lemaire
ICPAL, Univ. Lille, Inserm, U995-LIRIC-Lille Inflammation Research International Center, 3 rue du Professeur Laguesse BP83, F-59006 Lille, France.
Philippe
P
Chavatte
ICPAL, Univ. Lille, Inserm, U995-LIRIC-Lille Inflammation Research International Center, 3 rue du Professeur Laguesse BP83, F-59006 Lille, France. Electronic address: regis.millet@univ-lille2.fr.
Régis
R
Millet
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D000099252:Fatty Acid Amide Hydrolases
AEA; Cannabinoid receptors; FAAH inhibitor; PEA; PPAR-α