Syntheses and evaluation of fluorinated conformationally restricted analogues of GABA as potential inhibitors of GABA aminotransferase

Zhiyong Wang, Richard B Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Inhibition of γ-aminobutyric acid aminotransferase (GABA-AT) could raise the concentration of GABA, an inhibitory neurotransmitter in the human brain, and could have therapeutic applications for a variety of neurological diseases including epilepsy. Four fluorine-containing analogues of GABA with conformations restricted by a cyclohexane ring system were designed and synthesized, but unlike some of their five-membered ring counterparts, minimal inhibition of GABA-AT was observed. It is likely that the rigid chair conformation of these compounds cannot be accommodated well in the enzyme's active site.

Original languageEnglish (US)
Pages (from-to)2242-2252
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number7
DOIs
StatePublished - Apr 1 2006

Keywords

  • Conformationally restricted compounds
  • Enzyme inhibition
  • Fluorinated compounds
  • GABA
  • GABA-AT

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Syntheses and evaluation of fluorinated conformationally restricted analogues of GABA as potential inhibitors of GABA aminotransferase'. Together they form a unique fingerprint.

Cite this