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2,6-Disubstituted N-arylsulfonyl piperidines as gamma-secretase inhibitors |
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| Authors: | Pissarnitski Dmitri A Asberom Theodros Bara Thomas A Buevich Alex V Clader John W Greenlee William J Guzik Henry S Josien Hubert B Li Wei McEwan Michael McKittrick Brian A Nechuta Terry L Parker Eric M Sinning Lisa Smith Elizabeth M Song Lixin Vaccaro Henry A Voigt Johannes H Zhang Lili Zhang Qi Zhao Zhiqiang |
| Affiliation: | Department 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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