Fluorinated conformationally restricted γ-aminobutyric acid aminotransferase inhibitors

Hejun Lu, Richard B. Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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
Volume49
Issue number25
DOIs
StatePublished - Dec 14 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Fluorinated conformationally restricted γ-aminobutyric acid aminotransferase inhibitors'. Together they form a unique fingerprint.

  • Cite this