Design and discovery of C2-fluoroalkyl iminothiazine dioxides as BACE inhibitors

Autor:	Martin Dolmaski, Brandon M. Taoka, Jared N. Cumming, Maria S. Michener, Lynn A. Hyde, Jinsong Hao, Brad E. Smith, Hongwu Wang, Wen-Lian Wu, Matthew E. Kennedy, Dorthy Levorse, Peter Orth, Eric M. Parker
Rok vydání:	2022
Předmět:	Clinical Biochemistry Thiazines Administration Oral Pharmaceutical Science Biochemistry Amidine Structure-Activity Relationship chemistry.chemical_compound In vivo Drug Discovery Animals Aspartic Acid Endopeptidases Humans Enzyme Inhibitors Molecular Biology Cell potency Dose-Response Relationship Drug Molecular Structure biology Organic Chemistry Oxides Combinatorial chemistry Rats HEK293 Cells chemistry biology.protein Molecular Medicine Amyloid Precursor Protein Secretases Amyloid precursor protein secretase
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 56:128463
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2021.128463
Popis:	This paper describes the structure-activity-relationships of novel fluoroalkyl substituents at the C2 position of iminothiazine dioxide beta secretase inhibitors. Key discoveries include reduced amidine basicity and its effect on Pgp, cell potency, and efficacy in various preclinical in vivo efficacy animal models. Findings from these structure-activity-relationships are discussed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::984b2c3cec4c248c956651aadfe2ea29 https://doi.org/10.1016/j.bmcl.2021.128463 Zobrazit plný text záznamu Full Text from ScienceDirect