Fluorinated Conformationally Restricted γ-Aminobutyric Acid Aminotransferase Inhibitors
journal contributionposted on 14.12.2006, 00:00 by Hejun Lu, Richard B. Silverman
On the basis of the structures of several potent inhibitor molecules for γ-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molecules followed from a readily synthesized ketone intermediate. Three of the molecules were found to be irreversible inhibitors of GABA-AT with comparable or larger kinact/KI values than that of vigabatrin, a clinically used antiepilepsy drug, and the other three were reversible inhibitors. A possible mechanism for inactivation by one of the inactivators is proposed.