Design and synthesis of bicyclic heterocycles as potent γ-secretase modulators.
Daniel Oehlrich, Frederik J R Rombouts, Didier Berthelot, François P Bischoff, Michel A J De Cleyn, Libuse Jaroskova, Gregor Macdonald, Marc Mercken, Michel Surkyn, Andrés A Trabanco, Gary Tresadern, Sven Van Brandt, Adriana I Velter, Tongfei Wu, Harrie J M Gijsen
Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium. doehlric@its.jnj.com
Bioorganic & medicinal chemistry letters 2013 Sep 1The evolution of amide 3 into conformationally restricted bicyclic triazolo-piperidine 14-S as a γ-secretase modulator is described. This is a potential disease modifying anti-Alzheimer's drug which demonstrated high in vitro and in vivo potency against Aβ42 peptide, reduced lipophilicity and enhanced brain free fraction compared to the previous series. Copyright © 2013 Elsevier Ltd. All rights reserved.
Citation
Daniel Oehlrich, Frederik J R Rombouts, Didier Berthelot, François P Bischoff, Michel A J De Cleyn, Libuse Jaroskova, Gregor Macdonald, Marc Mercken, Michel Surkyn, Andrés A Trabanco, Gary Tresadern, Sven Van Brandt, Adriana I Velter, Tongfei Wu, Harrie J M Gijsen. Design and synthesis of bicyclic heterocycles as potent γ-secretase modulators. Bioorganic & medicinal chemistry letters. 2013 Sep 1;23(17):4794-800
PMID: 23890837
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