Synthesis and Biological Activity of New Derivatives of Isoindoline-1,3-dione as Non-Steroidal Analgesics

Abstract

A simple method for the synthesis of new derivatives of isoindoline-1,3-dione is developed in this study, which consists of the interaction of N-arylbenzenecarboximidamides with phthalic anhydride in benzene at reflux. It was found that carrying out the reaction without heating leads to the formation of monoacylation products—phthalic acid amides. The structure of the isolated substances was proved using 1H and 13C NMR spectroscopy. Acute toxicity and biological activity in silico were studied for all of the obtained compounds using the online programs GUSAR and PASS. For 2-(phenyl(phenylimino)methyl)isoindoline-1,3-dione and 2-((phenyl(phenylimino)methyl)carbamoyl)benzoic acid, an acute toxicity and biological activity in vivo was studied in laboratory mice. It was shown that the results of in silico and in vivo methods are comparable and indicate the low toxicity of the obtained compounds. It was revealed that 2-(phenyl(phenylimino)methyl)isoindoline-1,3-dione has a high analgesic activity, 1.6 times higher than the activity of the reference drug metamizole sodium.

Keywords

• isoindoline-1,3-diones
• 2-(phenyl(phenylimino)methyl)isoindoline-1,3-dione
• analgesic activity
• <i>N</i>-substituted derivatives of phthalimide
• non-steroidal analgesic