Synthesis, Cytostatic and Antibacterial Evaluations of Novel 1,2,3-Triazolyl-tagged Pyrimidine and Furo[2,3-d]pyrimidine Derivatives
| Autor: | Ljubica Glavaš-Obrovac, Marijana Jukić, Domagoj Drenjančević, Ana Ratković, Silvana Raić-Malić, Maja Stipković Babić, Tatjana Gazivoda Kraljević |
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| Rok vydání: | 2017 |
| Předmět: |
Trifluoromethyl
Pyrimidine biology 010405 organic chemistry Stereochemistry Triazole Sonogashira coupling General Chemistry 010402 general chemistry biology.organism_classification 01 natural sciences Coupling reaction 0104 chemical sciences HeLa chemistry.chemical_compound pyrimidine furo[2 3-d]pyrimidine Sonogashira cross-coupling reaction click chemistry antiproliferative antibacterial evaluations chemistry Click chemistry Moiety furo[2 3-d]pyrimidine |
| Zdroj: | Croatica Chemica Acta Volume 90 Issue 2 |
| ISSN: | 1334-417X 0011-1643 |
| DOI: | 10.5562/cca3165 |
| Popis: | C-5 alkynylated and N-1 alkylated pyrimidine derivatives were synthesized by N-alkylation reaction of 5-iodouracil in the presence of NaH, as a base, followed by Pd-catalyzed Sonogashira cross-coupling reaction of N-alkyl-5-iodouracil derivatives (1 and 2) with corresponding terminal alkynes. Intramolecular in situ O-heteroannulation ring closure of N-1-alkyl-C-5-alkynylpyrimidine derivatives (3 and 5) generated novel 6-substituted furo[2,3-d]pyrimidine derivatives (7 and 8). 1,4-Disubstituted 1,2,3-triazole tethered 5-alkynylpyrimidines (14–19) and 6-substituted furo[2,3-d]pyrimidines (20–22) were successfully prepared by the copper(I)-catalyzed click reaction of 5-iodo-N-1-propargylpyrimidine (2) using microwave irradiation, followed by Sonogashira cross-coupling reaction with corresponding terminal alkynes. In vitro antiproliferative activity of prepared compounds evaluated on human cancer cell lines cervix adenocarcinoma (HeLa), colon adenocarcinoma (CaCo-2), chronic myeloid leukemia in blast crisis (K562), Burkitt lymphoma (Raji) revealed that pyrimidine (19) and furo[2,3-d]pyrimidine (22) derivatives with 3,5-difluorophenyl at pyrimidine and furo[2,3-d]pyrimidine as well as p-(trifluoromethyl)phenyl at 1,2,3-triazole exhibited marked and selective inhibitory effects on the growth of K562 and Raji tumor cells. Antibacterial evaluations showed that pyrimidine derivative 14 substituted with p-tolylethynyl at C-5 of pyrimidine and benzyl at 1,2,3-triazole moiety was the most active of all evaluated compounds on the Gram positive bacterial strains Enterococcus faecalis. Further structure optimization of compounds 14, 19 and 22 is foreseen in order to obtain lead structural analogs with efficient and selective antitumoral and antibacterial activities. This work is licensed under a Creative Commons Attribution 4.0 International License. |
| Databáze: | OpenAIRE |
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