918547-84-9Relevant academic research and scientific papers
NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold
Zall, Andrea,Kieser, Daniel,Hoettecke, Nicole,Naumann, Eva C.,Thomaszewski, Binia,Schneider, Katrin,Steinbacher, Dirk T.,Schubenel, Robert,Masur, Stefan,Baumann, Karlheinz,Schmidt, Boris
, p. 4903 - 4909 (2011/10/04)
Modulation of γ-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived γ-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 ca
Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer γ-secretase modulators
Narlawar, Rajeshwar,Revuelta, Blanca I. Pérez,Haass, Christian,Steiner, Harald,Schmidt, Boris,Baumann, Karlheinz
, p. 7588 - 7591 (2007/10/03)
N-Sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of γ-secretase, which is associated with Alzheimer's disease. The introduction of a lipophilic substituent transformed the COX-2 inhibitor carprofen into a potent γ-secretase modulator. Several compounds (e.g., 9p, 11f) caused selective reduction of Aβ42 and an increase of Aβ38. The most active compounds displayed activities in the low micromolar range and no effect on the γ-secretase cleavage at the ε-site.
