Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor

  • J Med Chem. 2008 Aug 14;51(15):4632-40. doi: 10.1021/jm800566m.
Philip A Harris  1 ,  Amogh Boloor ,  Mui Cheung ,  Rakesh Kumar ,  Renae M Crosby ,  Ronda G Davis-Ward ,  Andrea H Epperly ,  Kevin W Hinkle ,  Robert N Hunter 3rd ,  Jennifer H Johnson ,  Victoria B Knick ,  Christopher P Laudeman ,  Deirdre K Luttrell ,  Robert A Mook ,  Robert T Nolte ,  Sharon K Rudolph ,  Jerzy R Szewczyk ,  Anne T Truesdale ,  James M Veal ,  Liping Wang ,  Jeffrey A Stafford
Affiliations
  • 1. GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. [email protected]
PMID: 18620382 DOI: 10.1021/jm800566m
Abstract

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.

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