3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors

The identification of a potent γ-secretase inhibitor, for example (ED 50 = 0.06 nM), is reported. The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent γ-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain Aβ in transgenic mouse models and thus have potential as possible treatments for Alzheimer’s disease.