C-5 Aryl Substituted Azaspirooxindolinones Derivatives: Synthesis and Biological Evaluation as Potential Inhibitors of Tec Family Kinases
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F21%3A73612817" target="_blank" >RIV/61989592:15110/21:73612817 - isvavai.cz</a>
Výsledek na webu
<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.202100699?src=getftr" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.202100699?src=getftr</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/ejoc.202100699" target="_blank" >10.1002/ejoc.202100699</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
C-5 Aryl Substituted Azaspirooxindolinones Derivatives: Synthesis and Biological Evaluation as Potential Inhibitors of Tec Family Kinases
Popis výsledku v původním jazyce
The interleukin-2-inducible kinase (ITK) and Bruton tyrosine kinase (BTK) are two crucial Tec family kinase members with important roles in the development of hematopoietic malignancies, autoimmune disorders and other diseases in humans. Thus, ITK and BTK are key targets for drug development. Spirooxindoles are important scaffolds for the synthesis of small molecules with broad and potent biological activities. In this study, we performed a structure-activity relationship study of a new series of 5 '-(benzo[d]([1,3])dioxol-5-yl)spiro[piperidine-4,3 '-pyrrolo([2,3-b])pyridin]-2 '(1 ' H)-one linked with N-acyl and C-5 aryl-substituted scaffolds in a panel of ITK and BTK cancer cell lines. Four compounds 11, 12, 14, and 15 showed high antiproliferative activity against ITK and BTK cell lines. Compounds 11 and 12 with a C-5 benzodioxole group and gem-dialkyl group attached to carbonyl on piperidine were highly effective in ITK-high Jurkat and CEM cell lines, and compound 14, a biotin analogue, was identified as a good inhibitor of BTK-high RAMOS cells. Compound 15 with cyclopropyl group attached to carbonyl on piperidine also showed good activity in ITK and BTK cell lines.
Název v anglickém jazyce
C-5 Aryl Substituted Azaspirooxindolinones Derivatives: Synthesis and Biological Evaluation as Potential Inhibitors of Tec Family Kinases
Popis výsledku anglicky
The interleukin-2-inducible kinase (ITK) and Bruton tyrosine kinase (BTK) are two crucial Tec family kinase members with important roles in the development of hematopoietic malignancies, autoimmune disorders and other diseases in humans. Thus, ITK and BTK are key targets for drug development. Spirooxindoles are important scaffolds for the synthesis of small molecules with broad and potent biological activities. In this study, we performed a structure-activity relationship study of a new series of 5 '-(benzo[d]([1,3])dioxol-5-yl)spiro[piperidine-4,3 '-pyrrolo([2,3-b])pyridin]-2 '(1 ' H)-one linked with N-acyl and C-5 aryl-substituted scaffolds in a panel of ITK and BTK cancer cell lines. Four compounds 11, 12, 14, and 15 showed high antiproliferative activity against ITK and BTK cell lines. Compounds 11 and 12 with a C-5 benzodioxole group and gem-dialkyl group attached to carbonyl on piperidine were highly effective in ITK-high Jurkat and CEM cell lines, and compound 14, a biotin analogue, was identified as a good inhibitor of BTK-high RAMOS cells. Compound 15 with cyclopropyl group attached to carbonyl on piperidine also showed good activity in ITK and BTK cell lines.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
<a href="/cs/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molekulární, buněčný a klinický přístup ke zdravému stárnutí</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
ISSN
1434-193X
e-ISSN
—
Svazek periodika
2021
Číslo periodika v rámci svazku
33
Stát vydavatele periodika
DE - Spolková republika Německo
Počet stran výsledku
11
Strana od-do
4630-4640
Kód UT WoS článku
000693198200008
EID výsledku v databázi Scopus
2-s2.0-85114303427