Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 53, Issue 1, Pages 499-503Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm901209q
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The discovery and optimization of potency and metabolic stability of a novel class of dihyroxyphenylisoindoline amides as Hsp90 inhibitors are presented. Optimization of a screening hit using structure-based design and modification of log D and chemical structural features led to the identification of a class of orally bioavailable non-quinone-containing Hsp90 inhibitors. This class is exemplified by 14 and 15, which possess improved cell potency and pharmacokinetic profiles compared with the original screening hit.
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