Discovery of (2, 4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1, 3-dihydroisoindol-2-yl] methanone (AT13387), a Novel Inhibitor of the Molecular …

…, R Feltell, E Figueroa, M Frederickson…

文献索引：Woodhead, Andrew J.; Angove, Hayley; Carr, Maria G.; Chessari, Gianni; Congreve, Miles; Coyle, Joseph E.; Cosme, Jose; Graham, Brent; Day, Philip J.; Downham, Robert; Fazal, Lynsey; Feltell, Ruth; Figueroa, Eva; Frederickson, Martyn; Lewis, Jonathan; McMenamin, Rachel; Murray, Christopher W.; O'Brien, M. Alistair; Parra, Lina; Patel, Sahil; Phillips, Theresa; Rees, David C.; Rich, Sharna; Smith, Donna-Michelle; Trewartha, Gary; Vinkovic, Mladen; Williams, Brian; Woolford, Alison J.-A. Journal of Medicinal Chemistry, 2010 , vol. 53, # 16 p. 5956 - 5969

全文：HTML全文

被引用次数: 128

摘要

Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure ...