Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

Abstract

In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides <b>2a</b>-<b>2p</b>. The compounds <b>2a</b>-<b>2p</b> were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-<i>c</i>]pyrrole scaffold (<b>1a</b>-<b>c</b>) with secondary amines and an excess of formaldehyde solution in C₂H₅OH. The structural properties of the compounds were characterized by ¹H NMR, ¹³C NMR FT-IR, MS, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound <b>2h</b>. The colorimetric inhibitor screening assay was used to obtain their potencies to inhibit COX-1 and COX-2 enzymes. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. Theoretical modeling was also applied to describe the binding properties of compounds towards COX-1 and COX-2 cyclooxygenase isoform. The data were supported by QSAR study.