Taking quinazoline as a general support-nog to design potent and selective kinase inhibitors: Application to FMS-like tyrosine kinase 3

Abstract

Molecular joinery: Herein we propose a concept for the design of selective kinase inhibitors. This de novo design method involves restricted fragment growth by using quinazoline as a general molecular support-nog. Application of this concept to the design of FMSlike tyrosine kinase 3 (FLT3) inhibitors led to a potent (IC50=7 nm) and selective FLT3 inhibitor. © 2010 Wiley-VCH Verlag GmbHand Co. KGaA, Weinheim.