Discovery of boronic acids as novel and potent inhibitors of fatty acid amide hydrolase.
A series of commercial phenyl-, heteroaryl-, alkyl-, and alkenylboronic acids were evaluated for their FAAH and MGL inhibitory activities. The compounds were generally selective for FAAH, with IC50 in the nanomolar or low-micromolar range. Eight of these compounds inhibited MGL with IC50 in the micromolar range. The most potent compound, phenylboronic acid with para-nonyl substituent (13), inhibited FAAH and MGL with IC50 of 0.0091 and 7.9 microM, respectively.
Minkkilä
Anna
A
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. anna.minkkila@uku.fi
Saario
Susanna M
SM
Käsnänen
Heikki
H
Leppänen
Jukka
J
Poso
Antti
A
Nevalainen
Tapio
T
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D000099252:Fatty Acid Amide Hydrolases