Author/Authors :
Nicholas Stock، نويسنده , , Benito Munoz، نويسنده , , Jonathan D.J. Wrigley، نويسنده , , Mark S. Shearman، نويسنده , , Dirk Beher، نويسنده , , James Peachey، نويسنده , , Toni L. Williamson، نويسنده , , Gretchen Bain، نويسنده , , Weichao Chen، نويسنده , , Xiaohui Jiang، نويسنده , , René St-Jacques، نويسنده , , Peppi Prasit، نويسنده ,
Abstract :
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.
