Biaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. Part I.

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Trova MP, Barnes KD, Barford C, Benanti T, Bielaska M, Burry L, Lehman JM, Murphy C, O'Grady H, Peace D, Salamone S, Smith J, Snider P, Toporowski J, Tregay S, Wilson A, Wyle M, Zheng X, Friedrich TD

Biaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. Part I.

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6608-12. doi: 10.1016/j.bmcl.2009.10.025. Epub 2009 Oct 12.

PubMed ID
19846305 [ View in PubMed
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Abstract

The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino group of the Cdk inhibitor roscovitine (2), maintained the potent Cdk inhibition demonstrated by roscovitine (2) as well as greatly improving the antiproliferative activity. A series of C-6 biarylmethylamino derivatives was prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions to provide compounds that displayed potent cytotoxic activity against tumor cell lines. In particular, derivative 21h demonstrated a >750-fold improvement in the growth inhibition of HeLa cells compared to roscovitine (2).

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
OlomoucineCyclin-dependent kinase 2IC 50 (nM)10000N/AN/ADetails
SeliciclibCyclin-dependent kinase 2IC 50 (nM)4600N/AN/ADetails
SeliciclibCyclin-dependent kinase 2IC 50 (nM)520N/AN/ADetails