1,4,6-Trisubstituted imidazo[4,5-c]pyridines as inhibitors of Bruton's tyrosine kinase

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F21%3A00545764" target="_blank" >RIV/61389030:_____/21:00545764 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/21:73608258
Result on the web
<a href="http://doi.org/10.1016/j.ejmech.2020.113094" target="_blank" >http://doi.org/10.1016/j.ejmech.2020.113094</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2020.113094" target="_blank" >10.1016/j.ejmech.2020.113094</a>

Result language
angličtina
Original language name
1,4,6-Trisubstituted imidazo[4,5-c]pyridines as inhibitors of Bruton's tyrosine kinase
Original language description
Herein, we report an efficient synthetic approach towards trisubstituted imidazo [4,5-c]pyridines designed as inhibitors of Bruton's tyrosine kinase (BTK). Two alternative synthetic routes for the simple preparation of desired compounds with variable substitutions at the N1, C4, C6 positions were introduced with readily available building blocks. Further, the developed synthetic approach was feasible for isomeric compounds bearing imidazo [4,5-b]pyridine scaffolds. In contrast to expectations based on previous studies, the imidazo [4,5-c]pyridine inhibitor exhibited a significantly higher activity against BTK compared to its imidazo [4,5-b]pyridine isomer. An inherent SAR study in the series of imidazo [4,5-c]pyridine compounds revealed a remarkably high tolerance of C6 substitutions for both hydrophobic and hydrophilic substituents. Preliminary cellular experiments indicated selective BTK targeting in Burkitt lymphoma and mantle cell lymphoma cell lines. The inhibitors could thus serve as starting points for further development, eventually leading to BTK inhibitors that could be used after ibrutinib failure.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30403 - Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions [pharmacogenomics, gene-based therapeutics])

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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