320337-46-0Relevant academic research and scientific papers
Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series
Petrov, Kimberly G.,Zhang, Yue-Mei,Carter, Malcolm,Cockerill, G. Stuart,Dickerson, Scott,Gauthier, Cassandra A.,Guo, Yu,Mook Jr., Robert A.,Rusnak, David W.,Walker, Ann L.,Wood, Edgar R.,Lackey, Karen E.
, p. 4686 - 4691 (2007/10/03)
Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme activity, but appeared to dramatically affect the cellular efficacy. The discovery of lapatinib emerged from this work.
Discovery and biological evaluation of potent dual ErbB-2/EGFR tyrosine kinase inhibitors: 6-Thiazolylquinazolines
Gaul, Micheal D.,Guo, Yu,Affleck, Karen,Cockerill, G. Stuart,Gilmer, Tona M.,Griffin, Robert J.,Guntrip, Stephen,Keith, Barry R.,Knight, Wilson B.,Mullin, Robert J.,Murray, Doris M.,Rusnak, David W.,Smith, Kathryn,Tadepalli, Sarva,Wood, Edgar R.,Lackey, Karen
, p. 637 - 640 (2007/10/03)
We have identified a novel class of 6-thiazolylquinazolines as potent and selective inhibitors of both ErbB-2 and EGFR tyrosine kinase activity, with IC50 values in the nanomolar range. These compounds inhibited the growth of both EGFR (HN5) and ErbB-2 (BT474) over-expressing human tumor cell lines in vitro. Using xenograft models of the same cell lines, we found that the compounds given orally inhibited in vivo tumor growth significantly compared with control animals.
