کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1377213 | 981974 | 2006 | 6 صفحه PDF | دانلود رایگان |
We describe a series of potent and selective oxindole–pyridine-based protein kinase B/Akt inhibitors. The most potent compound 11n in this series demonstrated an IC50 of 0.17 nM against Akt1 and more than 100-fold selectivity over other Akt isozymes. The selectivity against other protein kinases was highly dependent on the C-3 substitutions at the oxindole scaffold, with unsubstituted 9e or 3-furan-2-ylmethylene (11n) more selective and 3-(1H-pyrrol-2-yl)methylene (11f) or 3-(1H-imidazol-2-yl)methylene (11k) less selective. In a mouse xenograft model, 9d, 11f, and 11n inhibited tumor growth but with accompanying toxicity.
We discovered a series of potent and selective oxindole–pyridine-based protein kinase B/Akt inhibitors with an IC50 of 0.17 nM for the most potent compound. Correlation between in vitro selectivity and in vivo efficacy is also discussed.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 13, 1 July 2006, Pages 3424–3429