Tetracyclic sulfones as potent γ-secretase inhibitors: Synthesis and structure-activity relationship studies

Complex tetracyclic sulfones were designed as γ-secretase inhibitors and a stereoselective synthesis was achieved. γ-Secretase activity was seen predominately in the (−) enantiomeric series. Compounds such as 2a and 2b showed remarkable in vitro and in vivo potency.