4, 5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer

…, J Borgognoni, K Boxall, JE Cansfield…

文献索引：Brough, Paul A.; Aherne, Wynne; Barril, Xavier; Borgognoni, Jenifer; Boxall, Kathy; Cansfield, Julie E.; Cheung, Kwai-Ming J.; Collins, Ian; Davies, Nicholas G. M.; Drysdale, Martin J.; Dymock, Brian; Eccles, Suzanne A.; Finch, Harry; Fink, Alexandra; Hayes, Angela; Howes, Robert; Hubbard, Roderick E.; James, Karen; Jordan, Allan M.; Lockie, Andrea; Martins, Vanessa; Massey, Andrew; Matthews, Thomas P.; McDonald, Edward; Northfield, Christopher J.; Pearl, Laurence H.; Prodromou, Chrisostomos; Ray, Stuart; Raynaud, Florence I.; Roughley, Stephen D.; Sharp, Swee Y.; Surgenor, Allan; Walmsley, D. Lee; Webb, Paul; Wood, Mike; Workman, Paul; Wright, Lisa Journal of Medicinal Chemistry, 2008 , vol. 51, # 2 p. 196 - 218

全文：HTML全文

被引用次数: 303

摘要

Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure− activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4, 5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive ...