Synthesis and activity of 5-(aminomethyl)-1,3-cyclohexanediones: enolic analogs of .gamma.-aminobutyric acid
- 1 October 1985
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 28 (10), 1440-1446
- https://doi.org/10.1021/jm00148a012
Abstract
Eight 1,3-cyclohexanediones with an aminoalkyl side chain in the 5-position was synthesized as rigid enolic analogues of GABA (.gamma.-aminobutyric acid). Biochemical investigations about their abilities to displace [3H]baclofen [.beta.-(p-chlorophenyl)-.gamma.-aminobutyric acid] in binding studies or to inhibit the high-affinity sodium-dependent GABA uptake showed that these compounds were generally devoid of affinity for the two GABA receptors and for the GABA carrier. Only compound 1 exhibited a weak affinity in the GABA-A binding experiments (IC50 = 6.5 .times. 10-5 M). Graphic computer modeling was applied in an attempt to explain this activity in comparison to some reference GABA agonists. Electrophysiological studies on dorsal root ganglia (DRG) also excluded agonistic or antagonistic properties on GABA-A or GABA-B receptor models but pointed out an atypical prolongation of Ca2+-dependent action potential for compound 1.This publication has 11 references indexed in Scilit:
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