Discovery of novel aminoquinazolin-7-yl 6,7-dihydro-indol-4-ones as potent, selective inhibitors of heat shock protein 90

Autor:	Hanson Gunnar J, Philip F. Hughes, Barta Thomas E, Amy F. Barabasz, Briana Foley, James Marvin Veal, Jeffrey M. Partridge, Christopher John Markworth, Andy J. Ommen, Melanie Silinski, Steven E. Hall, John W. Rice, Paul M. Steed, Emilie D. Smith, Patrick Fadden, Kenneth He Huang, Wei Ma
Rok vydání:	2012
Předmět:	Models Molecular Indoles Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Plasma protein binding Biochemistry Small Molecule Libraries Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Heat shock protein Drug Discovery Quinazoline Humans Structure–activity relationship HSP90 Heat-Shock Proteins Molecular Biology Cell Proliferation biology Drug discovery Organic Chemistry Rational design Combinatorial chemistry Hsp90 chemistry Chaperone (protein) Quinazolines biology.protein Molecular Medicine Drug Screening Assays Antitumor Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 22:2550-2554
ISSN:	0960-894X
Popis:	A novel class of Hsp90 inhibitors, structurally distinct from previously reported scaffolds, was developed from rational design and optimization of a compound library screen hit. These aminoquinazoline derivatives, represented by compound 15 (SNX-6833) or 1-(2-amino-4-methylquinazolin-7-yl)-3,6,6-trimethyl-6,7-dihydro-1H-indol-4(5H)-one, selectively bind to Hsp90 and inhibit its cellular activities at concentrations as low as single digit nanomolar.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf7762235091c8d574857ff8ee4a9462 https://doi.org/10.1016/j.bmcl.2012.01.137 Zobrazit plný text záznamu Full Text from ScienceDirect