Document Report Card

ID: ALA1142716

Journal: J Med Chem

Title: 2-Hydroxy-4,6-diamino-[1,3,5]triazines: a novel class of VEGF-R2 (KDR) tyrosine kinase inhibitors.

Authors: Baindur N, Chadha N, Brandt BM, Asgari D, Patch RJ, Schalk-Hihi C, Carver TE, Petrounia IP, Baumann CA, Ott H, Manthey C, Springer BA, Player MR.

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 (IC(50) = 18 nM) and submicromolar inhibitory activity in a KDR-induced MAP kinase autophosphorylation assay in HUVEC cells (IC(50) = 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 IC(50) of 1 microM.

CiteXplore: 15771417

DOI: 10.1021/jm049372z