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 2a–2p. The compounds 2a–2p were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (1a–c) 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 2h. 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.

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

“…Redzicka et al. 84 designed and synthesised a series of N-substituted 3,4-pyrroledicarboximides. All compounds exhibited stronger inhibition of COX-2 than the reference drug (meloxicam) and compounds 69a and 69b ( Figure 10 ) were proven to be the most effective against COX-2 enzyme.…”

“…Replacement of aryl substituent in a series of piperazine derivatives with heteroaryl or cycloalkyl substitutes led to a significant reduction in COX-1 inhibition. Moreover, introduction of hydrophilic hydroxyethyl substitutes led to a decrease in the inhibitory activity in relation to both enzymes, while introduction of an OH group in a series of arylpiperidine derivatives significantly reduced COX-1 inhibition 84 .…”

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

“…More recently, Redzicka et al [ 136 ] reported design, synthesis, and anti-inflammatory activity of N-substituted 3,4-pyrroledicarboximides (65 a–k), (66) and (67 a–d) ( Fig. 19 ) .…”

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“…Triazoles have been shown to have confirmed eligible characteristics, like reduction conditions, high acid-base hydrolysis stability and metabolic degradation-resistance [8,9]. They include electrical, mechanical, magnetic, optical and corrosion properties far better than their individual components, because of their electroactive and conductive nature [10][11][12][13].…”