Conformationally-restricted vigabatrin analogs as irreversible and reversible inhibitors of gamma-aminobutyric acid aminotransferase.
Compounds that inhibit gamma-aminobutyric acid aminotransferase exhibit anticonvulsant activity; vigabatrin is a known irreversible inhibitor of this enzyme and anticonvulsant drug. Conformationally-restricted, five-membered- and six-membered-ring vigabatrin analogs were synthesized and tested as inhibitors of gamma-aminobutyric acid aminotransferase. Two monofluorinated compounds, 4 and 5, are time-dependent inhibitors of the enzyme, and their potencies are comparable to that of vigabatrin. Compounds 6 and 7 are weak reversible inhibitors.
Department of Chemistry, and Drug Discovery Program, Northwestern University, Evanston, IL 60208-3113, USA.
Yue
Y
Pan
Kristi
K
Calvert
Richard B
RB
Silverman
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D013552:Swine; D020888:Vigabatrin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin