Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series.
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Petrov KG, Zhang YM, Carter M, Cockerill GS, Dickerson S, Gauthier CA, Guo Y, Mook RA Jr, Rusnak DW, Walker AL, Wood ER, Lackey KE
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. Epub 2006 Jun 13.
- PubMed ID
- 16777410 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Lapatinib Epidermal growth factor receptor IC 50 (nM) 12 N/A N/A Details Lapatinib Receptor tyrosine-protein kinase erbB-2 IC 50 (nM) 10 N/A N/A Details