2-Hydroxy-4,6-diamino-[1,3,5]triazines: A Novel Class of VEGF-R2 (KDR) Tyrosine Kinase Inhibitors
Authors:
- 9 November 2004
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 48 (6) , 1717-1720
Abstract
2-Hydroxy-4,6-diamino-[1,3,5]triazines are described which are a novel class of potent inhibitors of the VEGF-R2 (flk-1/KDR) tyrosine kinase. 4-(Benzothiazol-6-ylamino)-6-(benzyl-isopropyl-amino)-[1,3,5]triazin-2-ol (14d) exhibited low nanomolar potency in the in vitro enzyme inhibition assay (IC50 = 18 nM) and submicromolar inhibitory activity in a KDR-induced MAP kinase autophosphorylation assay in HUVEC cells (IC50 = 280 nM), and also demonstrated good in vitro selectivity against a panel of growth factor receptor tyrosine kinases. Further, 14d showed antiangiogenic activity in an aortic ring explant assay by blocking endothelial outgrowths in rat aortas with an IC50 of 1 μM.Keywords
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