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

Department of Chemistry, Center for Drug Discovery and Chemical Biology, Northwestern University, Evanston, IL 60208-3113, USA.

Inhibition of gamma-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.

PMID: 16314106 [PubMed - indexed for MEDLINE]