Esters, retroesters, and a retroamide of palmitic acid: pool for the first selective inhibitors of N-palmitoylethanolamine-selective acid amidase.
Cyclohexyl hexadecanoate, hexadecyl propionate, and N-(3-hydroxypropionyl)pentadecanamide, respectively ester, retroester, and retroamide derivatives of N-palmitoylethanolamine, represent the first selective inhibitors of "N-palmitoylethanolamine hydrolase" described so far. These compounds are devoid of affinity for CB(1) and CB(2) receptors and characterized by high percentages of inhibition of N-palmitoylethanolamine-selective acid amidase (84.0, 70.5, and 76.7% inhibition at 100 microM, respectively) with much lower inhibitory effect on either fatty acid amide hydrolase or the uptake of anandamide.
Vandevoorde
Séverine
S
Unité de Chimie Pharmaceutique et de Radiopharmacie, Université Catholique de Louvain, Avenue Mounier, 73, UCL-CMFA 73.40, B-1200 Brussels, Belgium.
Tsuboi
Kazuhito
K
Ueda
Natsuo
N
Jonsson
Kent-Olov
KO
Fowler
Christopher J
CJ
Lambert
Didier M
DM
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D048588:Benzoxazines; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D016466:CHO Cells; D002121:Calcium Channel Blockers / Q000378:metabolism; D006224:Cricetinae; D003511:Cyclohexanols / Q000378:metabolism; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D009025:Morpholines / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism; D010168:Palmitates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism
D000577:Amides; D001095:Arachidonic Acids; D048588:Benzoxazines; D002121:Calcium Channel Blockers; C469526:Cnr2 protein, rat; D003511:Cyclohexanols; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004952:Esters; D007202:Indicators and Reagents; D009025:Morpholines; D009281:Naphthalenes; D010168:Palmitates; D053284:Polyunsaturated Alkamides; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000581:Amidohydrolases; C478603:N-palmitoylethanolamine-selective acid amidase; C078814:anandamide