Cyclic sulfamide γ-secretase inhibitors

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.

Graphical abstractA novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit.Figure optionsDownload full-size imageDownload as PowerPoint slide