Scaffold of the Cyclooxygenase-2 (COX-2) Inhibitor Carprofen Provides Alzheimer -Secretase Modulators

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• 作者：Rajeshwar Narlawar ; Blanca I. Pé ; rez Revuelta ; Christian Haass ; Harald Steiner ; Boris Schmidt ; Karlheinz Baumann
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：December 28, 2006
• 年：2006
• 卷：49
• 期：26
• 页码：7588 - 7591
• 全文大小：95K
• 年卷期：v.49,no.26(December 28, 2006)
• ISSN：1520-4804

文摘

N-Sulfonylated and N-alkylated carprofen derivatives wereinvestigated for their inhibition and modulation of -secretase, whichis associated with Alzheimer's disease. The introduction of a lipophilicsubstituent transformed the COX-2 inhibitor carprofen into a potent-secretase modulator. Several compounds (e.g., 9p, 11f) causedselective reduction of A₄₂ and an increase of A₃₈. The most activecompounds displayed activities in the low micromolar range and noeffect on the -secretase cleavage at the -site.