A NOVEL CLASS OF POTENT GAMMA-AMINOBUTYRIC-ACID AMINOTRANSFERASE INHIBITOR, 3-(HYDROXYAMINO)PROPYLAMINE AND ANALOGS

Hydroxyamino analogues of gamma-aminobutyric acid (GABA) were synthesi zed and evaluated for inhibitory activity toward gamma-aminobutyric ac id aminotransferase (GABA-T). The title compound, 3-(hydroxyamino)prop ylamine (HPA), showed a potent inhibitory activity. The inhibition is competitive with respect to GABA and the K-i value of GABA-T for HPA i s 0.4 mmol. The activity of inhibition is comparable to those of amino xyacetic acid and valproic acid. 3-(Hydroxyaminomethyl)piperidine (3HM P), a cyclic analogue of HPA, also showed a potent inhibitory activity , whereas 3-(methoxyamino)propylamine (OMe-HPA), 3-(N-hydroxy-N-methyl amino)propylamine (NMe-HPA) and 4-(hydroxyamino)piperidine (4HP) showe d weak activity. (C) 1997 Elsevier Science Ltd.