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Design and synthesis of a novel series of bicyclic heterocycles as potent γ-secretase modulators. 2012
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
Janssen Research & Development, Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium.
The design and the synthesis of several chemical subclasses of imidazole containing γ-secretase modulators (GSMs) is described. Conformational restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in vivo potency. This has resulted in the identification of benzimidazole 44a as a GSM with low nanomolar potency in vitro. In mouse, rat, and dog, this compound displayed the typical γ-secretase modulatory profile by lowering Aβ42 and Aβ40 levels combined with an especially pronounced increase in Aβ38 and Aβ37 levels while leaving the total levels of amyloid peptides unchanged.
Related Publications
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
January 2011,
Bioorganic & medicinal chemistry letters,
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
October 2011,
Bioorganic & medicinal chemistry letters,
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Didier Berthelot, and
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Garrett Minne, and
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Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
January 2014,
Bioorganic & medicinal chemistry letters,
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
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Journal of medicinal chemistry,
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Michel De Cleyn, and
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Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
June 2011,
ACS medicinal chemistry letters,
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
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Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
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ACS medicinal chemistry letters,
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
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Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
July 2010,
ACS medicinal chemistry letters,
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
May 2012,
Bioorganic & medicinal chemistry letters,
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
April 2012,
Bioorganic & medicinal chemistry letters,
Francois Bischoff, and
Didier Berthelot, and
Michel De Cleyn, and
Gregor Macdonald, and
Garrett Minne, and
Daniel Oehlrich, and
Serge Pieters, and
Michel Surkyn, and
Andrés A Trabanco, and
Gary Tresadern, and
Sven Van Brandt, and
Ingrid Velter, and
Mirko Zaja, and
Herman Borghys, and
Chantal Masungi, and
Marc Mercken, and
Harrie J M Gijsen
May 2015,
Bioorganic & medicinal chemistry,
