A novel class of potent gamma-aminobutyric acid aminotransferase inhibitor, 3-(hydroxyamino)propylamine and analogues.
Hydroxyamino analogues of gamma-aminobutyric acid (GABA) were synthesized and evaluated for inhibitory activity toward gamma-aminobutyric acid aminotransferase (GABA-T). The title compound, 3-(hydroxyamino)propylamine (HPA), showed a potent inhibitory activity. The inhibition is competitive with respect to GABA and the Ki value of GABA-T for HPA is 0.4 mmol. The activity of inhibition is comparable to those of aminoxyacetic acid and valproic acid. 3-(Hydroxyaminomethyl)piperidine (3HMP), a cyclic analogue of HPA, also showed a potent inhibitory activity, whereas 3-(methoxyamino)propylamine (OMe-HPA), 3-(N-hydroxy-N-methylamino)propylamine (NMe-HPA) and 4-(hydroxyamino)piperidine (4HP) showed weak activity.
Fushiya
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S
Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Kanazawa
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T
Nozoe
S
S
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D000613:Aminobutyrates / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D003959:Diamines / Q000138:chemical synthesis / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011437:Propylamines / Q000138:chemical synthesis / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology
C110104:3-(hydroxyamino)propylamine; D000613:Aminobutyrates; D003959:Diamines; D004791:Enzyme Inhibitors; D011437:Propylamines; C054822:4-N-hydroxy-2,4-diaminobutyric acid; D000625:Aminooxyacetic Acid; D014635:Valproic Acid; D000612:4-Aminobutyrate Transaminase