Design and synthesis of bicyclic heterocycles as potent γ-secretase modulators

Autor:	Adriana Ingrid Velter, Michel Anna Jozef De Cleyn, Frederik J. R. Rombouts, Sven Franciscus Anna Van Brandt, Didier Berthelot, Andrés A. Trabanco, Marc Mercken, Francois Paul Bischoff, Harrie J.M. Gijsen, Michel Surkyn, Tongfei Wu, Daniel Oehlrich, Libuse Jaroskova, Gregor James Macdonald, Gary Tresadern
Rok vydání:	2013
Předmět:	Models Molecular Stereochemistry Clinical Biochemistry Pharmaceutical Science Peptide Biochemistry chemistry.chemical_compound Mice Dogs Piperidines In vivo Alzheimer Disease Amide Drug Discovery Potency Animals Humans Molecular Biology chemistry.chemical_classification Bicyclic molecule Organic Chemistry Triazoles Bridged Bicyclo Compounds Heterocyclic Combinatorial chemistry In vitro chemistry Free fraction Drug Design Lipophilicity Microsomes Liver Molecular Medicine Amyloid Precursor Protein Secretases
Zdroj:	Bioorganicmedicinal chemistry letters. 23(17)
ISSN:	1464-3405
Popis:	The 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ccc1057bc559feaab7c8e5c34446e9c https://pubmed.ncbi.nlm.nih.gov/23890837 Zobrazit plný text záznamu Full Text from ScienceDirect