Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide (pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor
Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide (pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor
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DOI：
10.1021/jm800566m
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发表时间：
2008-08-14
影响因子：
7.3
通讯作者：
Stafford, Jeffrey A.
中科院分区：
文献类型：
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作者：
Harris, Philip A.;Boloor, Amogh;Stafford, Jeffrey A.
抑制血管内皮生长因子（VEGF）信号通路已成为癌症治疗最有前途的新方法之一。我们在本文中描述了从最初的筛选命中开始的关键步骤，导致帕唑帕尼，N-4-（2，3-二甲基-2H-吲唑-6-基）-N-4-甲基-N-2-（4-甲基-3-磺酰胺基苯基）-2，4-嘧啶二胺的发现，帕唑帕尼是一种有效的泛VEGF受体（VEGFR）抑制剂，正在临床开发用于肾细胞癌和其他实体瘤。
Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway has emerged as one of the most promising new approaches for cancer therapy. We describe herein the key steps starting from an initial screening hit leading to the discovery of pazopanib, N-4-(2,3-dimethyl-2H-indazol-6-yl)-N-4-methyl-N-2-(4-methyl-3-sulfonamidophenyl)-2,4-pyrimidinediamine, a potent pan-VEGF receptor (VEGFR) inhibitor under clinical development for renal-cell cancer and other solid tumors.