ANTIINFLAMMATORY 4,5-DIARYLPYRROLES .2. ACTIVITY AS A FUNCTION OF CYCLOOXYGENASE-2 INHIBITION

The antiinflammatory activity of a series of 2-substituted- and ed-4-( 4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl] -1H-pyrroles was previous ly shown by quantitative structure-activity relationship (QSAR) studie s to be correlated with the molar refractivity and inductive field eff ect of the 2-substituent and the lipophilicity of the 3-substituent. T he present study demonstrates that much ofthe antiinflammatory activit y of these pyrroles could be correlated with the inhibition of the ind ucible isoform of cyclooxygenase (COX2). Additional QSAR studies have been used to identify the molecular parameters necessary for maximizin g COX2 inhibition while simultaneously minimizing the inhibition of co nstitutively expressed cyclooxygenase-1. Such an effort should facilit ate the discovery and development of selective COX inhibitors that sho uld lead to safer nonsteroidal antiinflammatory drugs.