Fluorinated conformationally restricted γ-aminobutyric acid aminotransferase inhibitors

Hejun Lu, Richard B. Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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/K1 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.

Original languageEnglish (US)
Pages (from-to)7404-7412
Number of pages9
JournalJournal of Medicinal Chemistry
Issue number25
StatePublished - Dec 14 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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