The important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain.
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|Titolo:||Cyclooxygenase-2 Inhibitors. 1,5-Diarylpyrrol-3-acetic Esters with Enhanced Inhibitory Activity Toward Cyclooxygenase-2 and Improved Cyclooxygenase-2/Cyclooxygenase-1 Selectivity|
|Rivista:||JOURNAL OF MEDICINAL CHEMISTRY|
|Citazione:||M., B., G. C., P., G., P., S., S., S., F., M., R., et al. (2007). Cyclooxygenase-2 Inhibitors. 1,5-Diarylpyrrol-3-acetic Esters with Enhanced Inhibitory Activity Toward Cyclooxygenase-2 and Improved Cyclooxygenase-2/Cyclooxygenase-1 Selectivity. JOURNAL OF MEDICINAL CHEMISTRY, 50, 5403-5411.|
|Appare nelle tipologie:||1.1 Articolo in rivista|