Anilinotriazoles as potent gamma secretase modulators.

Velter, Adriana I; Bischoff, François P; Berthelot, Didier; De Cleyn, Michel; Oehlrich, Daniel; Jaroskova, Libuse; Macdonald, Gregor; Minne, Garrett; Pieters, Serge; Rombouts, Frederik; Van Brandt, Sven; Van Roosbroeck, Yves; Surkyn, Michel; Trabanco, Andrés A; Tresadern, Gary; Wu, Tongfei; Borghys, Herman; Mercken, Marc; Masungi, Chantal; Gijsen, Harrie

Velter, Adriana I; Bischoff, François P; Berthelot, Didier; De Cleyn, Michel; Oehlrich, Daniel; Jaroskova, Libuse; Macdonald, Gregor; Minne, Garrett; Pieters, Serge; Rombouts, Frederik; Van Brandt, Sven; Van Roosbroeck, Yves; Surkyn, Michel; Trabanco, Andrés A; Tresadern, Gary; Wu, Tongfei; Borghys, Herman; Mercken, Marc; Masungi, Chantal; Gijsen, Harrie.

Afiliação

Velter AI; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: ivelter@its.jnj.com.
Bischoff FP; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Berthelot D; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
De Cleyn M; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Oehlrich D; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Jaroskova L; Discovery Sciences, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Macdonald G; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Minne G; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Pieters S; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Rombouts F; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Van Brandt S; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Van Roosbroeck Y; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Surkyn M; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Trabanco AA; Neuroscience, Janssen Research & Development, Jarama 75, 45007 Toledo, Spain.
Tresadern G; Discovery Sciences, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Wu T; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Borghys H; Discovery Sciences, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Mercken M; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Masungi C; Discovery Sciences, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Gijsen H; Neuroscience, Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: hgijsen@its.jnj.com.

Bioorg Med Chem Lett ; 24(24): 5805-5813, 2014 Dec 15.

Article em En | MEDLINE | ID: mdl-25454273

ABSTRACT

ABSTRACT

The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile.

Assuntos

Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores; Compostos de Anilina/química; Triazóis/química; Secretases da Proteína Precursora do Amiloide/metabolismo; Peptídeos beta-Amiloides/química; Peptídeos beta-Amiloides/metabolismo; Compostos de Anilina/síntese química; Compostos de Anilina/metabolismo; Animais; Encéfalo/metabolismo; Desenho de Fármacos; Humanos; Camundongos; Camundongos Transgênicos; Ligação Proteica; Relação Estrutura-Atividade; Triazóis/síntese química; Triazóis/metabolismo

Palavras-chave

Alzheimer's disease; Anilinotriazoles; Gamma secretase modulators

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triazóis / Secretases da Proteína Precursora do Amiloide / Compostos de Anilina Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2014 Tipo de documento: Article

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