Pyrrolopyrimidine derivatives as dual COX-2/ACE2 inhibitors: design, synthesis, and anti-inflammatory evaluation

In this study, we report the design and synthesis of a new series of pyrrolopyrimidine derivatives developed as dual-target nonsteroidal anti-inflammatory agents (NSAIDs). The compounds were evaluated for anti-inflammatory properties, cyclooxygenase-1/2 (COX-1/COX-2) inhibitory activity, and angiotensin-converting enzyme 2 (ACE2)-blocking activity in lipopolysaccharide (lipopolysaccharide)-stimulated RAW264.7 cells. Among the synthesized molecules, compounds <b>5a</b> and <b>5b</b> showed potent dual inhibitory activity, which was supported by molecular docking and molecular dynamics simulations. These findings highlight the potential of selective COX-2 inhibitors with concurrent ACE2 blockade as a promising therapeutic approach for controlling inflammation and modulating pathways relevant to viral entry and other inflammation-associated disorders. While ACE2 inhibition has received particular attention in the context of recent viral infections, the broader anti-inflammatory efficacy of these derivatives supports their potential as multi-target drug candidates.