Novel 4-anilinoquinazolines with C-7 basic side chains: design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase …

LF Hennequin, ESE Stokes, AP Thomas…

Index: Hennequin, Laurent F.; Stokes, Elaine S. E.; Thomas, Andrew P.; Johnstone, Craig; Ple, Patrick A.; Ogilvie, Donald J.; Dukes, Michael; Wedge, Stephen R.; Kendrew, Jane; Curwen, Jon O. Journal of Medicinal Chemistry, 2002 , vol. 45, # 6 p. 1300 - 1312

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Citation Number: 325

Abstract

We have previously shown that 4-anilinoquinazolines can be potent inhibitors of vascular endothelial growth factor (VEGF) receptor (Flt-1 and KDR) tyrosine kinase activity. A novel subseries of 4-anilinoquinazolines that possess basic side chains at the C-7 position of the quinazoline nucleus have been synthesized. This subseries contains potent, nanomolar inhibitors of KDR (median IC50 0.02 μ M, range 0.001-0.04 μ M), which are comparatively ...