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

被引：20

作者：

Nemec, Vaclav ^{[1
,2
]}

Maier, Lukas ^{[1
,2
]}

Berger, Benedict-Tilman ^{[3
,4
]}

Chaikuad, Apirat ^{[3
,4
]}

Drapela, Stanislav ^{[2
,5
,6
]}

Soucek, Karel ^{[2
,5
,6
]}

Knapp, Stefan ^{[3
,4
]}

Paruch, Kamil ^{[1
,2
]}

机构：

[1] Masaryk Univ, Fac Sci, Dept Chem, Kamenice 5, Brno 62500, Czech Republic

[2] St Annes Univ Hosp Brno, Ctr Biomol & Cellular Engn, Int Clin Res Ctr, Pekarska 53, Brno 65691, Czech Republic

[3] Goethe Univ Frankfurt Main, Buchmann Inst Life Sci BMLS, Struct Genom Consortium SGC, Max von Laue Str 15, D-60438 Frankfurt, Germany

[4] Goethe Univ Frankfurt Main, Inst Pharmazeut Chem, Max von Laue Str 9, D-60438 Frankfurt, Germany

[5] Czech Acad Sci, Inst Biophys, Dept Cytokinet, Kralovopolska 135, Brno 61265, Czech Republic

[6] Masaryk Univ, Fac Sci, Dept Expt Biol, Kotlarska 267-2, Brno 61137, Czech Republic

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 215卷

基金：

巴西圣保罗研究基金会; 加拿大创新基金会;

关键词：

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

D O I：

10.1016/j.ejmech.2021.113299

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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.

引用

页数：8

共 37 条

[1] The crystal structure of the protein kinase HIPK2 reveals a unique architecture of its CMGC-insert region [J].