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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Petrov, KG; Zhang, Y-M; Carter, M; Cockerill, GS; Dickerson, S; Gauthier, CA; Guo, Y; Mook, RA; Rusnak, DW; Walker, AL; Wood, ER; Lackey, KE

Published Date

  • September 1, 2006

Published In

Volume / Issue

  • 16 / 17

Start / End Page

  • 4686 - 4691

PubMed ID

  • 16777410

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2006.05.090


  • eng

Conference Location

  • England