Preparation of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines as RET kinase inhibitors

Journal of Medicinal Chemistry
Peter DinérMorten Grøtli

Abstract

A series of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines have been designed, synthesized, and evaluated as RET protein kinase inhibitors. On the basis of docking results, a small library of pyrazolopyrimidine compounds with an extended hydrophobic side arm was synthesized. The most promising of the compounds (7a) displayed efficient inhibition in vitro and good selectivity when tested on a panel of kinases. Furthermore, 7a inhibited GDNF-induced RET phosphorylation of ERK1/2 in MCF-7 breast cancer cells at concentrations as low as 100 nM.

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Citations

Mar 20, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Negera AbdissaMáté Erdélyi
Aug 25, 2015·Scientific Reports·David BlimanMorten Grøtli
May 7, 2015·Scientific Reports·Rubén FerreiraMorten Grøtli
Apr 14, 2017·Bioorganic & Medicinal Chemistry Letters·Chengyan WangAo Zhang
Aug 12, 2014·European Journal of Medicinal Chemistry·Meng Li, Bao-Xiang Zhao
Jun 12, 2018·Archiv der Pharmazie·András DemjénIván Kanizsai
Nov 26, 2015·Acta Crystallographica. Section E, Crystallographic Communications·Mohammed El FalLahcen El Ammari
Nov 28, 2020·Future Medicinal Chemistry·Cong-Cong JiaZhao-Peng Liu
Sep 17, 2014·Journal of Natural Products·Ivan GumulaMáté Erdélyi

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