Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core

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作   者：

Nemec, Vaclav;  Maier, Lukas;  Berger, Benedict-Tilman;  Chaikuad, Apirat;  Drapela, Stanislav;  Soucek, Karel;  Knapp, Stefan;  Paruch, Kamil; 

作者机构：

Czech Republic;  Fac Sci;  Kamenice 5;  Brno 62500;  St Annes Univ Hosp Brno;  Masaryk Univ;  Ctr Biomol & Cellular Engn;  Int Clin Res Ctr;  Max von Laue;  Brno 65691;  Dept Chem;  Struct Genom Consortium SGC;  Pekarska 53;  Goethe Univ Frankfurt Main;  Buchmann Inst Life Sci BMLS; 

关键词：

MU1210;  CLK;  Kinase;  2-b]pyridine;  MU1787;  Inhibitor;  Furo[3;  HIPK;  MU135; 

期刊名称：

European Journal of Medicinal Chemistry: Chimie Therapeutique

i s s n：

0223-5234

年卷期：

2021 年 215 卷

页   码：

摘   要：

The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, we report flexible synthesis of 3,5-disubstituted furo [3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro [3,2-b]pyridine. This methodology allowed efficient second-generation synthesis of the state-of-the-art chemical biology probe for CLK1/2/4 MU1210, and identification of the highly selective inhibitors of HIPKs MU135 and MU1787 which are presented and characterized in this study, including the X-ray crystal structure of MU135 in HIPK2. chemical biology probe (c) 2021 Published by Elsevier Masson SAS.