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Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series |
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| Authors: | Petrov Kimberly G Zhang Yue-Mei Carter Malcolm Cockerill G Stuart Dickerson Scott Gauthier Cassandra A Guo Yu Mook Robert A Rusnak David W Walker Ann L Wood Edgar R Lackey Karen E |
| Affiliation: | GlaxoSmithKline, Research Triangle Park, NC, USA. |
| 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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