Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer γ-secretase modulators
J Med Chem 49(26): 7588-91
Perez Revuelta BI
|Type of Publication:||Journal Article|
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.