Design, synthesis, and structure-activity relationship studies of N-arylsulfonyl morpholines as γ-secretase inhibitors

Design and synthesis of cis-2,6-disubstituted N-arylsulfonyl morpholines as novel gamma-secretase inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. Several different small alkyl groups are installed on the left-hand side to lower the CYP3A4 liability while maintaining excellent in vitro potency. (C) 2010 Elsevier Ltd. All rights reserved.