Saftić, Dijana (2013) Novel 1,4-Disubstituted 1,2,3-Triazole Derivatives of the Purine and Pyrimidine Series: Synthesis and Biological Evaluation. Doctoral thesis, Faculty of Science.
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Abstract
As a part of investigation aimed to identify new small molecules with improved biological properties in the in vitro screening for antitumor activity the 1,4-disubstituted 1,2,3-triazole derivatives of guanosine, acyclovir (5, 10–12, and 14), uracil (19, 20, and 25–33), N-1-sulfonyl uracil (34–41) and uridine (46–55) were prepared. New synthetic method for preparation of unstable 8-hydrazine guanosine 3 by using microwave reactor (MR) was developed. Product 3 was converted into 8-azido guanosine 4 in the reaction with NaN3. The latter compound was used in numerous experiments directed to find optimal reaction conditions for Cu(I) catalyzed 1,3-dipolar cycloaddition reaction (CuAAC) with terminal alkynols. By the latter method 1,2,3-triazole acyclovir derivatives (10–12, and 14) were prepared. In order to prepare C5-triazolyl pyrimidine derivatives starting 5-etynyl uracil 18 and 5-etynyl uridine 45 (MR) derivatives were synthesized using Sonogashira coupling; the azides were generated in situ from alkyl halogenides and NaN3 or 5-azido sugar 24 was used. By subsequent CuAAC reaction the C5-triazolyl uracil (19, 25–28, 30–33) and uridine (46–48, 50–53, 55) (MR) derivatives were prepared in excellent yields. Condensation reaction of 1,4-disubstituted C5 triazole uracil derivatives (19, 28–31) with DBU and sulfonyl chlorides gave the respective N-1-sulfonyl uracil derivatives (34, 37–39, and 41) in very good yields, while condensation reaction with N1' unsubstituted triazole derivative 20 resulted with only trace amounts of 35 and 36. All 1,4-disubstituted 1,2,3-triazole derivatives were tested for the antiproliferative activity on the panel of eight cell lines (MDCK, HeLa, CaCo-2, NCI-H358, K562, Jurkat, HuT 78, and Raji), and detailed analysis of structure/activity relationship (SAR) was presented.
| Item Type: | Thesis (Doctoral thesis) | ||||||||
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| Uncontrolled Keywords: | uracil, uridine ; N-sulfonyl uracil ; click reaction ; 1,2,3-triazole ; antitumor activity | ||||||||
| Subjects: | NATURAL SCIENCES NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry |
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| Divisions: | Division of Organic Chemistry and Biochemistry | ||||||||
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| Depositing User: | Dijana Pavlović Saftić | ||||||||
| Date Deposited: | 05 Oct 2022 08:24 | ||||||||
| URI: | http://fulir.irb.hr/id/eprint/7535 |
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