Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and c-erbB-2

Described herein is the design and synthesis of indazolylaminopyridopyrimidines and quinazolines as inhibitors of the class 1 tyrosine kinase receptor family. Data is presented for N 4-(1-benzyl-1 H-indazol-5-yl)- N 6, N 6-dimethylpyrido[3,4- d]pyrimidine-4,6-diamine 3B. This compound inhibited EGFr and c-erbB-2 enzymes selectively over other kinases. It inhibited the proliferation of a range of tumour cell lines in vitro and the growth of BT474 xenografts in SCID mice. The identification of the c-erbB-2/EGFr inhibitor GW974 is described.