Design, Synthesis, and Biological Activity of a Difluoro-Substituted, Conformationally Rigid Vigabatrin Analogue as a Potent γ-Aminobutyric Acid Aminotransferase Inhibitor

Citations Over TimeTop 24% of 2003 papers

Abstract

Previously it was found that a conformationally rigid analogue (2) of the epilepsy drug vigabatrin (1) did not inactivate gamma-aminobutyric acid aminotransferase (GABA-AT). A cyclic compound with an exocyclic double bond (6) was synthesized and was found to inactivate GABA-AT, but only in the absence of 2-mercaptoethanol. The corresponding difluoro-substituted analogue (14) was synthesized and was shown to be a very potent time-dependent inhibitor, even in the presence of 2-mercaptoethanol.

Related Papers

• → OV329, a novel highly potent γ‐aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala‐kindled rats(2021)18 cited
• → Development of tolerance to the anticonvulsant effect of vigabatrin in amygdala-kindled rats(1992)38 cited
• → Single systemic dose of vigabatrin induces early proconvulsant and later anticonvulsant effect in rats(2001)10 cited
• → Effects of increasing doses of vigabatrin on platelet γ-aminobutyric acid-transaminase and brain γ-aminobutyric acid in rats(1999)5 cited
• → Anticonvulsant Effect of Systemically Administered γ-Aminobutyric Acid (GABA)-Containing Liposomes in Rats Induced to Seizure by Amygdaloid Electrical Stimulation(1992)4 cited