Cyclic sulfamide γ-secretase inhibitors

Abstract A novel series of N -alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N -alkyl groups and amines resulting in the identification of N -trifluoroethyl-substituted cyclic sulfamides with good in vitro and in vivo γ-secretase activity. One compound with subnanomolar activity elicited a reduction in brain Aβ40 after oral dosing in APP-YAC mice.