Cyclic sulfamide γ-secretase inhibitors

Autor:	Earl E. Clarke, Timothy Harrison, Jonathan D. Best, Bindi Sohal, Mirlinda Biba, Mark S. Shearman, Christopher J. Welch, Andrew Madin, Jonathan D.J. Wrigley, Huw D. Lewis, José L. Castro, Joanne Clare Hannam, Dirk Beher, Nancy N. Tsou, Tim Sparey
Rok vydání:	2005
Předmět:	Clinical Biochemistry Administration Oral Pharmaceutical Science Biochemistry Chemical synthesis Inhibitory Concentration 50 Mice Structure-Activity Relationship chemistry.chemical_compound Heterocyclic Compounds In vivo Endopeptidases Drug Discovery Amyloid precursor protein Animals Aspartic Acid Endopeptidases Protease Inhibitors Molecular Biology Sulfamide Brain Chemistry Amyloid beta-Peptides biology Organic Chemistry Biological activity Combinatorial chemistry In vitro chemistry Enzyme inhibitor biology.protein Molecular Medicine Amyloid Precursor Protein Secretases Sulfonic Acids Amyloid precursor protein secretase
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 15:4212-4216
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2005.06.084
Popis:	A novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N-alkyl groups and amines resulting in the identification of N-trifluoroethyl-substituted cyclic sulfamides with good in vitro and in vivo γ-secretase activity. One compound with subnanomolar activity elicited a reduction in brain Aβ40 after oral dosing in APP-YAC mice.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24d8ea2266ac589e3f3e4a96128239e5 https://doi.org/10.1016/j.bmcl.2005.06.084 Zobrazit plný text záznamu Full Text from ScienceDirect