N-(5-chloro-1, 3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl) ethoxy]-5-(tetrahydro-2 h-pyran-4-yloxy) quinazolin-4-amine, a novel, highly selective, orally available, …

…, C Lambert-van der Brempt, R Morgentin…

Index: Hennequin, Laurent F.; Allen, Jack; Breed, Jason; Curwen, Jon; Fennell, Michael; Green, Tim P.; Lambert-Van Der Brempt, Christine; Morgentin, Remy; Norman, Richard A.; Olivier, Annie; Otterbein, Ludovic; Ple, Patrick A.; Warin, Nicolas; Costello, Gerard Journal of Medicinal Chemistry, 2006 , vol. 49, # 22 p. 6465 - 6488

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Citation Number: 250

Abstract

Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5 ...

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