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

…, GS Cockerill, S Dickerson, CA Gauthier, Y Guo…

Index: 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. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 17 p. 4686 - 4691

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Citation Number: 126

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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