Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective
Kinase Inhibitors and Effective Modulators of the Hedgehog
Pathway

J 2019

Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway

NĚMEC, Václav, Michaela HYLSOVÁ, Lukáš MAIER, Jana FLEGEL, Sonja SIEVERS et. al.

Basic information

Original name

Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway

Authors

NĚMEC, Václav (203 Czech Republic, belonging to the institution), Michaela HYLSOVÁ (203 Czech Republic, belonging to the institution), Lukáš MAIER (203 Czech Republic, belonging to the institution), Jana FLEGEL (276 Germany), Sonja SIEVERS (276 Germany), Slava ZIEGLER (276 Germany), Martin SCHRÖDER (276 Germany), Benedict-Tilman BERGER (276 Germany), Apirat CHAIKUAD (764 Thailand), Barbora VALČÍKOVÁ (203 Czech Republic, belonging to the institution), Stjepan ULDRIJAN (203 Czech Republic, belonging to the institution), Stanislav DRÁPELA (203 Czech Republic), Karel SOUČEK (203 Czech Republic), Hebert WALDMANN (276 Germany), Stefan KNAPP (276 Germany) and Kamil PARUCH (203 Czech Republic, guarantor, belonging to the institution)

Edition

Angewandte Chemie International Edition, Weinheim, Wiley-VCH, 2019, 1433-7851

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10400 1.4 Chemical sciences

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 12.959

RIV identification code

RIV/00216224:14310/19:00109101

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1002/anie.201810312

UT WoS

000456260200017

Keywords in English

biological activity; chemical probes; heterocycles; inhibitors; kinases

Abstract

V originále

Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

LM2015063, research and development project

Name: Národní infrastruktura chemické biologie (Acronym: CZ-OPENSCREEN)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1087/2018, interní kód MU

Name: Molekulární a buněčná biologie pro biomedicínské vědy

Investor: Masaryk University, Category A

MUNI/E/0456/2018, interní kód MU

Name: Finální profilace vysoce účinných a selektivních inhibitorů proteinových kináz CLK a CK1

Investor: Masaryk University, Promoting quality excellence

Citovat

NĚMEC, Václav, Michaela HYLSOVÁ, Lukáš MAIER, Jana FLEGEL, Sonja SIEVERS, Slava ZIEGLER, Martin SCHRÖDER, Benedict-Tilman BERGER, Apirat CHAIKUAD, Barbora VALČÍKOVÁ, Stjepan ULDRIJAN, Stanislav DRÁPELA, Karel SOUČEK, Hebert WALDMANN, Stefan KNAPP and Kamil PARUCH. Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway. Angewandte Chemie International Edition. Weinheim: Wiley-VCH, 2019, vol. 58, No 4, p. 1062-1066. ISSN 1433-7851. Available from: https://dx.doi.org/10.1002/anie.201810312.

@article{1494217,
   author = {Němec, Václav and Hylsová, Michaela and Maier, Lukáš and Flegel, Jana and Sievers, Sonja and Ziegler, Slava and Schröder, Martin and Berger, BenedictandTilman and Chaikuad, Apirat and Valčíková, Barbora and Uldrijan, Stjepan and Drápela, Stanislav and Souček, Karel and Waldmann, Hebert and Knapp, Stefan and Paruch, Kamil},
   article_location = {Weinheim},
   article_number = {4},
   doi = {http://dx.doi.org/10.1002/anie.201810312},
   keywords = {biological activity; chemical probes; heterocycles; inhibitors; kinases},
   language = {eng},
   issn = {1433-7851},
   journal = {Angewandte Chemie International Edition},
   title = {Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway},
   url = {https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.201810312},
   volume = {58},
   year = {2019}
}

TY  - JOUR
ID  - 1494217
AU  - Němec, Václav - Hylsová, Michaela - Maier, Lukáš - Flegel, Jana - Sievers, Sonja - Ziegler, Slava - Schröder, Martin - Berger, Benedict-Tilman - Chaikuad, Apirat - Valčíková, Barbora - Uldrijan, Stjepan - Drápela, Stanislav - Souček, Karel - Waldmann, Hebert - Knapp, Stefan - Paruch, Kamil
PY  - 2019
TI  - Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway
JF  - Angewandte Chemie International Edition
VL  - 58
IS  - 4
SP  - 1062-1066
EP  - 1062-1066
PB  - Wiley-VCH
SN  - 14337851
KW  - biological activity
KW  - chemical probes
KW  - heterocycles
KW  - inhibitors
KW  - kinases
UR  - https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.201810312
L2  - https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.201810312
N2  - Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.
ER  -

NĚMEC, Václav, Michaela HYLSOVÁ, Lukáš MAIER, Jana FLEGEL, Sonja SIEVERS, Slava ZIEGLER, Martin SCHRÖDER, Benedict-Tilman BERGER, Apirat CHAIKUAD, Barbora VALČÍKOVÁ, Stjepan ULDRIJAN, Stanislav DRÁPELA, Karel SOUČEK, Hebert WALDMANN, Stefan KNAPP and Kamil PARUCH. Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway. \textit{Angewandte Chemie International Edition}. Weinheim: Wiley-VCH, 2019, vol.~58, No~4, p.~1062-1066. ISSN~1433-7851. Available from: https://dx.doi.org/10.1002/anie.201810312.

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