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

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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