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 A beta(42) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining A beta(42) inhibition. Methylflurbiprofen 6 exhibited similar in vitro A beta(42) 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. (C) 2006 Elsevier Ltd. All rights reserved.