Cs2CO3-Promoted Alkylation of 3-Cyano-2(1H)-Pyridones: Anticancer Evaluation and Molecular Docking.
Chempluschem
; : e202400172, 2024 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-38840415
ABSTRACT
Herein, a Cs2CO3-promoted N-alkylation of 3-cyano-2(1H)-pyridones containing alkyl groups with diverse alkyl halides to synthesize N-alkyl-2-pyridones over O-alkylpyridines is reported. The use of alkyl dihalides resulted in complex mixtures of N- and O-alkylated products. The primary factor influencing regioselectivity in these reactions is the electronic effects of substituents on the 2(1H)-pyridone ring, as evidenced by the preferential formation of O-alkylpyridines upon the introduction of aryl groups. Remarkably, we efficiently employed CuAAC and Ti(Oi-Pr)4-catalyzed amidation reactions to functionalize N-alkyl-2-pyridones containing propargyl and ester groups, leading to the synthesis of 1,2,3-triazoles and amides, respectively. Moreover, O-alkylpyridines 10 b and 10 d displayed remarkable selectivity toward the A-498 renal cancer cell line with growth inhibition percentages (%GI) of 54.75 and 67.64, respectively. The binding modes of compounds 10 b and 10 d to the PIM-1 kinase enzyme were determined through molecular docking studies.
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01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Chempluschem
Ano de publicação:
2024
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Article