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

被引：56

作者：

Baindur, N ^{[1
]}

Chadha, N ^{[1
]}

Brandt, BM ^{[1
]}

Asgari, D ^{[1
]}

Patch, RJ ^{[1
]}

Schalk-HiHi, C ^{[1
]}

Carver, TE ^{[1
]}

Petrounia, IP ^{[1
]}

Baumann, CA ^{[1
]}

Ott, H ^{[1
]}

Manthey, C ^{[1
]}

Springer, BA ^{[1
]}

Player, MR ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Discovery, Cranbury, NJ 08512 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 06期

关键词：

D O I：

10.1021/jm049372z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M.

引用

页码：1717 / 1720

页数：4

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