Concise synthesis and CDK/GSK inhibitory activity of the missing 9-azapaullones

Bioorganic & Medicinal Chemistry Letters
David P PowerStephen J Connon

Abstract

A remarkably concise, chromatography-free route to the parent compound of the paullone family of cyclin-dependent kinase (CDK) inhibitors is reported. A similar strategy allowed the synthesis of the hitherto missing 9-azapaullone and its protonated, N-oxidised and N-alkylated derivatives. Screening studies identified an active and strongly selective inhibitor of CDK9/cyclin T.

References

Nov 3, 1989·Science·L H Hartwell, T A Weinert
Mar 21, 2002·Nature Reviews. Cancer·M Malumbres, M Barbacid
Sep 19, 2002·Trends in Pharmacological Sciences·Marie KnockaertLaurent Meijer
Mar 5, 2003·Journal of Cell Science·Bradley W Doble, James R Woodgett
Nov 19, 2004·Nature·Michael B Kastan, Jiri Bartek
Feb 8, 2005·Chembiochem : a European Journal of Chemical Biology·Conrad KunickThomas Lemcke
May 11, 2005·Expert Opinion on Investigational Drugs·Peter M Fischer, Athos Gianella-Borradori
Jul 22, 2008·Drug Discovery Today·Campbell McInnes
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Nov 4, 2009·Nature Cell Biology·Marcos MalumbresDebra J Wolgemuth

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Citations

Feb 25, 2014·European Journal of Medicinal Chemistry·Audrey GalludNicolas Masurier
Jul 2, 2016·Chemical Communications : Chem Comm·Hayden A SharmaKarl A Scheidt
Jan 31, 2012·Organic & Biomolecular Chemistry·Sara SotoÁngel R de Lera
Apr 27, 2021·European Journal of Medicinal Chemistry·Ravikumar AkunuriSrinivas Nanduri

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