N-Sulfonylated and N-alkylated carbazolyloxyacetic acids were investigated for the inhibition and modulation of the Alzheimer's disease associated γ-secretase. The introduction of a lipophilic substituent, which may vary from arylsulfone to alkyl, turned 2- carbazolyloxyacetic acids into potent γ-secretase modulators. This resulted in the selective reduction of Aβ42 and an increase of the less aggregatory Aβ38 fragment by several ...