کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1378020 | 981992 | 2007 | 7 صفحه PDF | دانلود رایگان |
We have developed a series of novel potent ortho-substituted azole derivatives active against kinases VEGFR-1 and VEGFR-2. Both specific and dual ATP-competitive inhibitors of VEGFR-2 were identified. Kinase activity and selectivity could be controlled by varying the arylamido substituents at the azole ring. The most specific molecule (17) displayed >10-fold selectivity for VEGFR-2 over VEGFR-1. Compound activities in enzymatic and cell-based assays were in the range of activities for reported clinical and development candidates (IC50 < 100 nM), including Novartis’ PTK787 (Vatalanib)™. High permeability of active compounds across the Caco-2 cell monolayer (>30 × 10−5 cm/min) is indicative of their potential for intestinal absorption upon oral administration.
A novel series of potent ortho-substituted azole derivatives active against kinases VEGFR-1 and VEGFR-2 is described. Both specific and dual ATP-competitive inhibitors of VEGFR-2 were identified.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 5, 1 March 2007, Pages 1369–1375