Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Prime side chromane-containing inhibitors

Autor:	David F. Nakamura, Hing L. Sham, John-Michael Sauer, Dean R. Artis, Lany Ruslim, Ted Yednock, Michael A. Pleiss, Gary Probst, Marc Adler, Minghua Sun, Louis Brogley, Michael S. Dappen, Roy K. Hom, Michel Maillard, Nanhua Yao, Simeon Bowers, Andrei W. Konradi, Jay S. Tung, Raymond A. Ng, Andrea Gailunas, Wes Zmolek, Kevin P. Quinn, Fang Lawrence Y, Varghese John, R. Jeffrey Neitz, Michael P. Bova
Rok vydání:	2013
Předmět:	Models Molecular Binding Sites Chemistry Stereochemistry Organic Chemistry Clinical Biochemistry Substituent Pharmaceutical Science Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Drug Design Drug Discovery Ethylamines Aspartic Acid Endopeptidases Molecular Medicine Structure–activity relationship Chromane Amyloid Precursor Protein Secretases Chromans Enzyme Inhibitors Selectivity Molecular Biology Cells Cultured
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 23:4674-4679
ISSN:	0960-894X
Popis:	The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1′ region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2′ substituent of chromane–HEA(s) with polar substituents provided improvements in the compound’s in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7bd8b1a206227969363800a4024a00c https://doi.org/10.1016/j.bmcl.2013.06.006 Zobrazit plný text záznamu Full Text from ScienceDirect