2-((1H-Azol-1-yl)methyl)-N-arylbenzamides: Novel dual inhibitors of VEGFR-1/2 kinases

详细信息    查看全文

• 作者：Alexander S. Kiselyov ; Marina Semenova ; Victor V. Semenov and Evgueni Piatnitski
• 关键词：Vascular endothelial growth factor receptor 2 ; Receptor tyrosine kinase ; Dual kinase inhibitor ; Angiogenesis ; 2-((1H-Azol-1-yl)methyl)-N-arylbenzyl amides
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2006
• 出版时间：15 March 2006
• 年：2006
• 卷：16
• 期：6
• 页码：1726-1730
• 全文大小：184 K

文摘

Novel potent derivatives of (azol-1-yl)methyl-N-arylbenzamides with improved solubility (>3 mM) are described as ATP-competitive inhibitors of vascular endothelial growth factor receptor 2 (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity reaching IC₅₀ < 100 nM in the enzymatic assay. The compounds also inhibit the related tyrosine kinase, VEGFR-1, with similar potencies. Several compounds containing bulky lipophilic substituents at the benzamide pharmacophore yielded 10- to 17-fold selectivity for the VEGFR-2 versus VEGFR-1 kinase.