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Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series

2006; Elsevier BV; Volume: 16; Issue: 17 Linguagem: Inglês

10.1016/j.bmcl.2006.05.090

1464-3405

Kimberly G. Petrov, Yuemei Zhang, Malcolm Carter, G. Stuart Cockerill, Scott H. Dickerson, Cassandra Gauthier, Yu Guo, Robert A. Mook, David W. Rusnak, Ann L. Walker, Edgar R. Wood, Karen Lackey,

HER2/EGFR in Cancer Research

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.