The type I receptor tyrosine kinases (RTKs) are involved in various aspects of 
cell growth, survival, and differentiation. Among the known RTKs, the epidermal 
growth factor receptor (EGFR) and ErbB-2 (HER-2) are two widely studied proteins 
that are prototypic members of the ErbB family which also includes ErbB-3 
(Her-3) and ErbB-4 (Her-4). Overexpression of ErbB-2 and EGFR has been 
associated with aggressive disease and poor patient prognosis in a range of 
human tumour types (e.g. breast, lung, ovarian, prostate, and squamous carcinoma 
of head and neck). Disruption of signal transduction of these kinases has been 
shown to have an antiproliferative effect. Various approaches have been 
developed to target the ErbB signalling pathways including monoclonal antibodies 
(trastuzumab/Herceptin™ and cetuximab/Erbitux™) directed against the receptor, 
and synthetic tyrosine kinase inhibitors (gefitinib/Iressa™ and 
erlotinib/Tarceva™). Since many tumours overexpress ErbB receptors, simultaneous 
targeting of multiple ErbB receptors therefore becomes a promising approach to 
cancer treatment. Lapatinib (Tykerb™), a potent dual EGFR/ErbB-2 inhibitor, was 
approved for the treatment of ErbB-2-positive breast cancer. Despite years of 
intensive research on EGFR inhibitors, there is a surprising dearth of 
chemically distinct small inhibitors with a high degree of selectivity. There is 
also a need for new scaffolds due to the recent finding of EGFR mutations which 
render the kinase resistant to gefinitib and erlotinib. The structures under 
study will be quinazolines with different substituents. The structure-activity 
relationships and biological evaluation of compounds published during the last 
four years will be reviewed herein.