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

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

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2550-4

Authors: Huang KH, Barta TE, Rice JW, Smith ED, Ommen AJ, Ma W, Veal JM, Fadden RP, Barabasz AF, Foley BE, Hughes PF, Hanson GJ, Markworth CJ, Silinski M, Partridge JM, Steed PM, Hall SE

Abstract
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.

PMID: 22386527 [PubMed - indexed for MEDLINE]

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