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Zhang, Lin; Fan, Junhua; Vu, Khang; Hong, Kevin; Le Brazidec, Jean-Yves; Shi, Jiandong; Biamonte, Marco; Busch, David J; Lough, Rachel E; Grecko, Roy; Ran, Yingqing; Sensintaffar, John L; Kamal, Adeela; Lundgren, Karen; Burrows, Francis J; Mansfield, Robert; Timony, Gregg A; Ulm, Edgar H; Kasibhatla, Srinivas R; Boehm, Marcus F
Journal of medicinal chemistry, 08/2006, Letnik: 49, Številka: 17Journal Article
We report on the discovery of benzo- and pyridino- thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7‘-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28−150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2-ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H- purin-6-ylamine).
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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