ortho-Substituted azoles as selective and dual inhibitors of VEGF receptors 1 and 2.
Article Details
- CitationCopy to clipboard
Kiselyov AS, Piatnitski EL, Samet AV, Kisliy VP, Semenov VV
ortho-Substituted azoles as selective and dual inhibitors of VEGF receptors 1 and 2.
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1369-75. Epub 2006 Dec 2.
- PubMed ID
- 17188873 [ View in PubMed]
- Abstract
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 (> 30x10(-5) cm/min) is indicative of their potential for intestinal absorption upon oral administration.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Vatalanib Vascular endothelial growth factor receptor 1 IC 50 (nM) 54 N/A N/A Details Vatalanib Vascular endothelial growth factor receptor 2 IC 50 (nM) 21 N/A N/A Details Vatalanib Vascular endothelial growth factor receptor 2 IC 50 (nM) 140 N/A N/A Details