Journal of medicinal chemistry · 2014
Synthesis and evaluation of phosphorus containing, specific CDK9/CycT1 inhibitors.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Németh Gábor, Greff Zoltán, Sipos Anna, Varga Zoltán, Székely Rita, Sebestyén Mónika, Jászay Zsuzsa, Béni Szabolcs, Nemes Zoltán, Pirat Jean-Luc, Volle Jean-Noël, Virieux David, Gyuris Ágnes, Kelemenics Katalin, Ay Eva, Minarovits Janos, Szathmary Susan, Kéri György, Orfi László
Аннотация
Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate, and phosphinate moieties were synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell-based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds against CDKs and other kinases was tested. The best compound was shown to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity.