Sulfonamide derivatives of bridgehead substituted bicyclo[4.2.1]nonanes as γ-secretase inhibitors

Bridgehead substituted derivatives of bicyclo[4.2.1]nonanes were synthesized and shown to be potent inhibitors of γ-secretase. Two related series were synthesized to explore the SARs. More potent compounds were found in the non-benzofused series compared with the benzofused series. One compound from each series showed good exposure in the hepatic portal vein (HPV) following oral dosing to rats.