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

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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.