ω-Fluoromethyl Analogues of ω-Amino Acids as Irreversible Inhibitors of 4-Aminobutyrate: 2- Oxoglutarate Aminotransferase

Abstract— ω -Monofluoromethyl and ω-difluoromethyl analogues of the known substrates of GABA-T, β -alanine, γ -aminobutyric acid, and 5-aminopentanoic acid, are time dependent inhibitors of purified 4-aminobutyrate: 2-oxoglutarate aminotransferase (GABA-T). The inhibitory activity decreases with increasing chain length. In vitro , inhibitory activity decreases with increasing fluorine substitution of the methyl group. In vivo , β -difluoromethyl- β -alanine and 2,4-difluoro-3-aminobutyric acid are the most potent GABA-T inhibitors ever reported. Trifluoromethyl derivatives are devoid of GABA-T inhibitory activity in vitro or in vivo.