Design, synthesis and <i>in vitro</i> and <i>in vivo</i> biological evaluation of flurbiprofen amides as new fatty acid amide hydrolase/cyclooxygenase-2 dual inhibitory potential analgesic agents

Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is competitive, reversible inhibitor of with Ki value 13 nM which inhibits COX activity in substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits hydrophobic pocket the ACB region FAAH, binds to COX-2 similarly flurbiprofen. In vivo studies indicated at dose 10 mg/kg, was active models prolonged (formalin) neuropathic (chronic constriction injury) pain reduced spinal expression iNOS, COX-2, NFκB model. Thus, present study identifies as dual-action FAAH/substrate-selective anti-inflammatory analgesic animal models. These findings underscore potential usefulness such compounds.