Discovery of novel 5-alkynyl-4-anilinopyrimidines as potent, orally active dual inhibitors of EGFR and Her-2 tyrosine kinases.

Article Details

Citation

Copy to clipboard

Suzuki N, Shiota T, Watanabe F, Haga N, Murashi T, Ohara T, Matsuo K, Omori N, Yari H, Dohi K, Inoue M, Iguchi M, Sentou J, Wada T

Discovery of novel 5-alkynyl-4-anilinopyrimidines as potent, orally active dual inhibitors of EGFR and Her-2 tyrosine kinases.

Bioorg Med Chem Lett. 2012 Jan 1;22(1):456-60. doi: 10.1016/j.bmcl.2011.10.103. Epub 2011 Nov 6.

PubMed ID

22101132 [ View in PubMed

]

Abstract

5-Alkenyl or 5-alkynyl-4-anilinopyrimidines were prepared and evaluated for in vitro inhibition of EGFR/Her-2 kinase activity and the growth of tumor cell lines (BT474 and N87). Several of these compounds inhibited the growth of BT474 and N87 at concentrations below 200nM. Structure-activity relationship studies revealed a critical role for the 5-alkynyl moieties. The representative compound 19 exhibited significant antitumor potency in a mouse xenograft model.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Erlotinib	Epidermal growth factor receptor	IC 50 (nM)	1	N/A	N/A	Details
Lapatinib	Epidermal growth factor receptor	IC 50 (nM)	10	N/A	N/A	Details
Lapatinib	Receptor tyrosine-protein kinase erbB-2	IC 50 (nM)	9	N/A	N/A	Details