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Synthesis and evaluation of phosphorus containing, specific CDK9/CycT1 inhibitors.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Németh G,Greff Z,Sipos A,Varga Z,Székely R,Sebestyén M,Jászay Z,Béni S,Nemes Z,Pirat JL,Volle JN,Virieux D,Gyuris Á,Kelemenics K,Ay E,Minarovits J,Szathmary S,Kéri G,Orfi L

doi

10.1021/jm401742r

subject

Has Abstract

pub_date

2014-05-22 00:00:00

pages

3939-65

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

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