期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 54, 期 18, 页码 6234-6253出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm200553w
关键词
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资金
- NIH [CA120458, T32 GM008545]
- ACS Division of Medicinal Chemistry
The design, synthesis, and biological evaluation of conformationally constrained coumermycin Al analogues are reported. Compounds were evaluated against both breast cancer (SKBr3 and MCF7) and prostate cancer (PC3 mm2, A549, and HT29) cell lines. Non-noviosylated coumermycin Al analogues that manifest potent antiproliferative activity resulting from Hsp90 inhibition are provided, wherein replacement of the stereochemically complex noviose sugar with readily available piperidine rings resulted in similar to 100 fold increase in antiproliferative activities as compared to coumermycin Al, producing small molecule Hsp90 inhibitors that exhibit nanomolar activities.
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