title: Identification of a novel arylpiperazine scaffold for fatty acid amide hydrolase inhibition with improved drug disposition properties.
abstract: We herein describe the systematic approach used to develop new analogues of compound 2, recently identified as a potent and selective fatty acid amide hydrolase (FAAH) inhibitor. Aiming at identifying new scaffolds endowed with improved drug disposition properties with respect to the phenylpyrrole-based lead, we subjected it to two different structural modification strategies. This process allowed the identification of derivatives 4b and 5c as potent, reversible and non-competitive FAAH inhibitors.
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, Via Aldo Moro, 53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
authors.forename: Samuele
authors.initials: S
authors.lastname: Maramai
authors.forename: Patrizia
authors.initials: P
authors.lastname: Minetti
authors.forename: Diana
authors.initials: D
authors.lastname: Celona
authors.forename: Raffaella
authors.initials: R
authors.lastname: Napolitano
authors.forename: Franco
authors.initials: F
authors.lastname: Borsini
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
authors.forename: Filomena
authors.initials: F
authors.lastname: Fezza
authors.forename: Lucio
authors.initials: L
authors.lastname: Merlini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dallavalle
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001667:Binding, Competitive; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D011758:Pyrroles; D000099252:Fatty Acid Amide Hydrolases; C581769:ST3913