| Autor: |
Baindur N; Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, New Jersey 08512, USA., 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 |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2005 Mar 24; Vol. 48 (6), pp. 1717-20. |
| DOI: |
10.1021/jm049372z |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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