Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 16, Issue 8, Pages 2219-2223Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2006.01.033
Keywords
cyclooxygenase; Alzheimer's disease
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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.
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