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

  • Bioorg Med Chem Lett. 2006 Sep 1;16(17):4686-91. doi: 10.1016/j.bmcl.2006.05.090.
Kimberly G Petrov  1 ,  Yue-Mei Zhang ,  Malcolm Carter ,  G Stuart Cockerill ,  Scott Dickerson ,  Cassandra A Gauthier ,  Yu Guo ,  Robert A Mook Jr ,  David W Rusnak ,  Ann L Walker ,  Edgar R Wood ,  Karen E Lackey
Affiliations
  • 1. GlaxoSmithKline, Research Triangle Park, NC, USA.
PMID: 16777410 DOI: 10.1016/j.bmcl.2006.05.090
Abstract

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.

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