Synthesis and monoamine oxidase inhibitory activities of 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole derivatives

Ten new 1-thiocarbamoyl-3-(phenyl and/or 4-substituted phenyl)-5-(3,4-dimethoxyphenyl and/or 2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives were synthesized by reacting 1,3-diphenylpropen-1-ones and thiosemicarbazide. The chemical structures of the compounds were verified by means of their IR, 1H-NMR, ESI-MS spectroscopic data and elementary analyses. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in-vitro tests. Monoamine oxidase was isolated and purified from the mitochondrial extracts of rat-liver homogenates and human platelets. Monoamine oxidase inhibitory activities of the compounds were compared with pargyline and clorgyline. Most of the compounds inhibited the total activity of rat liver homogenates. The monoamine oxidase-A inhibitory effects of 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole were detected as potent as clorgyline. Selective and irreversible inhibition of rat liver monoamine oxidase-A by synthesized compounds have promising features for designing the new selective monoamine oxidase A inhibitors as potent and reliable anti-depressants in the future.