Author/Authors :
Kimberly G. Petrov، نويسنده , , Yue Mei Zhang، نويسنده , , J. Malcolm Carter، نويسنده , , G. Stuart Cockerill، نويسنده , , Scott Dickerson، نويسنده , , Cassandra A. Gauthier، نويسنده , , Yu Guo، نويسنده , , Robert A. Mook Jr.، نويسنده , , David W. Rusnak، نويسنده , , Ann L. Walker، نويسنده , , Edgar R. Wood، نويسنده , , Karen E. Lackey، نويسنده ,
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.
Keywords :
ErbB-1 tyrosine kinase inhibitors , ErbB-2 tyrosine kinase inhibitors , EGFR kinase inhibitors , Quinazoline , Lapatinib
