N-Substituted (Hexahydro)-1H-isoindole-1,3(2H)-dione Derivatives: New Insights into Synthesis and Characterization

Novel phthalimide derivatives, namely N-(1,3-dioxoisoindolin-2-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (1a) and N-(1,3-dioxoisoindolin-2-yl)thiophene-2-carboxamide (1b), and hexahydrophthalimide derivative N-(1,3-dioxohexahydro-1H-isoindol-2(3H)-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (2), have been synthesized. The phthalimide derivatives were synthesized from phthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide or thiophene-2-carbohydrazide, and the hexahydrophthalimide derivative has been synthesized from hexahydrophthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide. The chemical structures of the compounds are elucidated by Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectra. The new in vitro antioxidant activities of the obtained substances were evaluated using the DPPH method. All tested compounds showed antioxidative activity, the most active compound being 1b. Bioinformatics tools were used for the prediction of pharmacokinetics and pharmacodynamics profiles. Our results showedthat all compounds have a suitable intestinal absorption rate, good BBB and CNS permeabilities and have as molecular targets MAO B, COX-2 and NF-KB, important for antioxidant activities.

Automated summary

Novel phthalimide derivatives and hexahydrophthalimide derivative have been successfully synthesized and their chemical structures were elucidated. The compounds exhibited antioxidative activity, with compound 1b being the most active. Bioinformatics analysis predicted their pharmacokinetics and pharmacodynamics profiles, showing good intestinal absorption, BBB and CNS permeabilities, and important molecular targets for antioxidant activity.