Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer γ-secretase modulators

被引：36

作者：

Narlawar, Rajeshwar

Perez Revuelta, Blanca I.

Haass, Christian

Steiner, Harald

Schmidt, Boris

Baumann, Karlheinz

机构：

[1] Tech Univ Darmstadt, Clemens Schopf Inst Chem & Biochem, D-64287 Darmstadt, Germany

[2] Univ Munich, Dept Biochem, Lab Alzheimers & Parkinsons Dis Res, Adolf Butenandt Inst, D-80336 Munich, Germany

[3] F Hoffmann La Roche & Co Ltd, Preclin Res CNS, Div Pharmaceut, CH-4070 Basel, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 26期

关键词：

D O I：

10.1021/jm0610200

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

N-Sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of gamma-secretase, which is associated with Alzheimer's disease. The introduction of a lipophilic substituent transformed the COX-2 inhibitor carprofen into a potent gamma-secretase modulator. Several compounds (e.g., 9p, 11f) caused selective reduction of A beta(42) and an increase of A beta(38). The most active compounds displayed activities in the low micromolar range and no effect on the gamma-secretase cleavage at the epsilon-site.

引用

页码：7588 / 7591

页数：4

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