Abstract
A novel piperidine series of γ-secretase inhibitors, potentially useful for the treatment of Alzheimer’s disease, is disclosed. SAR investigation revealed the requirement for cis-stereochemistry of the substituents attached to the core, which resulted in the chair-like diaxial conformation of the piperidine ring. The series was optimized to provide inhibitors with IC 50’s in the single-digit nanomolar range. Absolute stereochemistry of the active enantiomer was assigned.
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