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

被引：308

作者：

Harris, Philip A.

Boloor, Amogh

Cheung, Mui

Kumar, Rakesh

Crosby, Renae M. ^{[1
]}

Davis-Ward, Ronda G. ^{[1
]}

Epperly, Andrea H. ^{[1
]}

Hinkle, Kevin W. ^{[1
]}

Hunter, Robert N., III ^{[1
]}

Johnson, Jennifer H. ^{[1
]}

Knick, Victoria B. ^{[1
]}

Laudeman, Christopher P. ^{[1
]}

Luttrell, Deirdre K.

Mook, Robert A. ^{[1
]}

Nolte, Robert T. ^{[1
]}

Rudolph, Sharon K. ^{[1
]}

Szewczyk, Jerzy R. ^{[1
]}

Truesdale, Anne T.

Veal, James M.

Wang, Liping ^{[1
]}

Stafford, Jeffrey A.

机构：

[1] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 15期

关键词：

D O I：

10.1021/jm800566m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：4632 / 4640

页数：9

共 21 条

[11] Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity [J].