Benzylamides and piperazinoarylamides of ibuprofen as fatty acid amide hydrolase inhibitors.
FAAH inhibition
Ibuprofen amides
endocannabinoids
fatty acid amide hydrolase
induced fit docking
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
29
1
2019
pubmed:
29
1
2019
medline:
8
5
2019
Statut:
ppublish
Résumé
Fatty Acid Amide Hydrolase (FAAH) is a serine hydrolase that plays a key role in controlling endogenous levels of endocannabinoids. FAAH inhibition is considered a powerful approach to enhance the endocannabinoid signalling, and therefore it has been largely studied as a potential target for the treatment of neurological disorders such as anxiety or depression, or of inflammatory processes. We present two novel series of amide derivatives of ibuprofen designed as analogues of our reference FAAH inhibitor Ibu-AM5 to further explore its structure-activity relationships. In the new amides, the 2-methylpyridine moiety of Ibu-AM5 was substituted by benzylamino and piperazinoaryl moieties. The obtained benzylamides and piperazinoarylamides showed FAAH inhibition ranging from the low to high micromolar potency. The binding of the new amides in the active site of FAAH, estimated using the induced fit protocol, indicated arylpiperazinoamides binding the ACB channel and the cytosolic port, and benzylamides binding the ACB channel.
Identifiants
pubmed: 30688118
doi: 10.1080/14756366.2018.1532418
pmc: PMC6352954
doi:
Substances chimiques
Amides
0
Enzyme Inhibitors
0
Piperazine
1RTM4PAL0V
Amidohydrolases
EC 3.5.-
fatty-acid amide hydrolase
EC 3.5.1.-
Ibuprofen
WK2XYI10QM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-576Références
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