The preparation and sar of 4-(anilino), 4-(phenoxy), and 4-(thiophenoxy)-quinazolines: Inhibitors of p56 lck and EGF-R tyrosine kinase activity

Abstract

We report herein our preliminary results of a SAR study of quinazoline-based inhibitors of p56 lck and EGF-R tyrosine kinase activity. 1 The most potent inhibitor of p56 lck identified, RPR-108518A ( 10), has an IC 50 of 0.50 μM. The 3-chlorophenoxy- and 3-chlorothiophenoxy- derivatives 5 and 6 were also shown to be extremely potent EGF-R inhibitors.