3-Aminobenzoic Acid Analogues as a Novel GABA-at Inhibitors: Synthesis, Pharmacological Evaluation and Molecular Docking Studies

Abstract

In present investigation we attempt to synthesized and evaluated rigid GABA analogues as potential anticonvulsant. Substituted 3-aminobenzoic acid derivatives (A to H) were obtained is good yields by the reaction of substituted aniline with amino protected (phthalimide) 3-aminobenzoic acid. Among 8 tested molecule five molecules found active in scPTZ model of anticonvulsant screening. The compounds A; 3-(1, 3-dioxo-2, 3-dihydro-1H-isoindol-2yl)-N-(2-nitrophenyl) benzamide and D; (N-(3-chlorophenyl)-3-(1, 3-dioxo-2, 3-dihydro-1H-isoindol-2yl) benzamide) were found active at the dose level of 100 mg/kg, the compound F;N-(2-chloro-4-nitrophenyl)-3-(1, 3-dioxo-2, 3-dihydro-1H-isoindol-2yl) benzamide and G;N- (4-bromophenyl)-3-(1, 3-dioxo-2, 3-dihydro-1H-isoindol-2yl) benzamide found to possess moderate anticonvulsant potential. Further compound B; N-(2-bromo-2, 4-dinitrophenyl)-3-(1, 3-dioxo-2, 3-dihydro1H-isoindol-2yl) benzamidewas found also safe in long spam of time i.e. 4hr.,this result clearly indicated compound B(-5.69) are most and equivalent to diazepam(-5.68), Inhibition constant (Ki) values of compound B and diazepam, 67.79 μm and 68.93 μm respectively. however compound A and D were found protective at the dose level of 100 mg/kg in long duration of action. But the compounds F and G filed in long term treatment.Moreover the animal recovery was more than 90 %.