Design, synthesis and structure–activity relationship of novel [3.3.1] bicyclic sulfonamide-pyrazoles as potent γ-secretase inhibitors

Autor:	Chris M. Semko, Danielle L. Aubele, Guriqbal S. Basi, Wes Zmolek, Gary Probst, Matthew N. Mattson, Elizabeth F. Brigham, Erich Goldbach, Karina Wong, William A Wallace, John-Michael Sauer, Hing L. Sham, Lan K. Nguyen, Michael P. Bova, Andrei W. Konradi, Albert W. Garofalo, Susanna S. Hemphill, Darren B. Dressen, Kevin P. Quinn, Minghua Sun, Anh P. Truong, Simeon Bowers
Rok vydání:	2011
Předmět:	Stereochemistry Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Mice Inbred Strains Biochemistry Amyloid beta-Protein Precursor Inhibitory Concentration 50 Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Peptide synthesis Animals Structure–activity relationship γ secretase Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Sulfonamides Amyloid beta-Peptides Bicyclic molecule Chemistry Organic Chemistry Combinatorial chemistry Sulfonamide Design synthesis Drug Design Molecular Medicine Amyloid Precursor Protein Secretases Selectivity Heterocyclic Compounds 3-Ring
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:5791-5794
ISSN:	0960-894X
Popis:	The structure–activity relationship (SAR) of a novel, potent and metabolically stable series of sulfonamide-pyrazoles that attenuate β-amyloid peptide synthesis via γ-secretase inhibition is detailed herein. Sulfonamide-pyrazoles that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via a single PO dose, as well as sulfonamide-pyrazoles that exhibit selectivity for inhibition of APP versus Notch processing by γ-secretase, are highlighted.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c797a2f9e3d425d83f37dc2fbd3a6ac https://doi.org/10.1016/j.bmcl.2011.08.008 Zobrazit plný text záznamu Full Text from ScienceDirect