Synthesis of an aryloxy oxo pyrimidinone library that displays ALK-selective inhibition.

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Slavish PJ, Price JE, Jiang Q, Cui X, Morris SW, Webb TR

Synthesis of an aryloxy oxo pyrimidinone library that displays ALK-selective inhibition.

Bioorg Med Chem Lett. 2011 Aug 1;21(15):4592-6. doi: 10.1016/j.bmcl.2011.05.103. Epub 2011 Jun 12.

PubMed ID

21708465 [ View in PubMed

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Abstract

We report the synthesis of a pyrimidinone library that targets anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase. This library was generated in three steps from a versatile commercially available starting material. Some compounds within this library showed single digit micromolar inhibition of ALK in vitro, while showing minimal inhibition of other homologous insulin receptor family kinases including the human insulin receptor kinase (IRK), at the highest concentrations investigated. We also present initial ALK structure-activity relationships for this library.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Crizotinib	Hepatocyte growth factor receptor	IC 50 (nM)	0.78	N/A	N/A	Details