The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer’s disease modifying agent

The subtle modification of a selection of Aβ42 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining Aβ42 inhibition. Methylflurbiprofen 6 exhibited similar in vitro Aβ42 inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer’s disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clinical development.

The subtle modification of a selection of Aβ42 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl derivatives, was anticipated to ablate their cyclooxygenase activity whilst maintaining potency at Aβ42 inhibition. One such compound, methylflurbiprofen, exhibited similar in vitro Aβ42 inhibition to its parent NSAID Flurbiprofen and was further evaluated in the TG2576 mouse model of Alzheimer’s disease and an animal model of gastro-intestinal (GI) impairment.Figure optionsDownload as PowerPoint slide