title: Lipophilic amines as potent inhibitors of N-acylethanolamine-hydrolyzing acid amidase.
abstract: N-Acylethanolamines (NAEs) including N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine are endogenous lipid mediators. These molecules are degraded to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH) or NAE-hydrolyzing acid amidase (NAAA). Lipophilic amines, especially pentadecylamine (2c) and tridecyl 2-aminoacetate (11b), were found to exhibit potent NAAA inhibitory activities (IC(50)=5.7 and 11.8μM), with much weaker effects on FAAH. These simple structures would provide a scaffold for further improvement in NAAA inhibitory activity.
authors.affiliation: Department of Organic Chemistry for Life Science, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan. y-yamano@kobepharma-u.ac.jp
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamano
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hozaki
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Jin
authors.forename: Natsuo
authors.initials: N
authors.lastname: Ueda
authors.forename: Akimori
authors.initials: A
authors.lastname: Wada
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D015394:Molecular Structure; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; C575349:tridecyl 2-aminoacetate; C575350:pentadecylamine; D000581:Amidohydrolases; C046993:N-acylethanolamine amidohydrolase; C575348:N-acylethanolamine-hydrolyzing acid amidase, rat; D005998:Glycine