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Updated: Jul 19, 2026

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
Published on: January 25, 2018
2,6-Disubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors
Dmitri A Pissarnitski1, Theodros Asberom, Thomas A Bara
1Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033, USA. Dmitri.Pisaarnitski@spcorp.com
Abstract:
A novel piperidine series of gamma-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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