Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents

Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/−)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations.

(−)-10b: R = 3-F, COX-2 affinity: 0.075 μM, COX-1/COX-2 selectivity >1300. (+)-10c: R = 4-OCH3, COX-2 affinity: 0.079 μM, COX-1/COX-2 selectivity >1200. Celecoxib (1b): COX-2 affinity: 0.06 μM, COX-1/COX-2 selectivity: 61.7.Figure optionsDownload as PowerPoint slide