Synthesis, Structural Studies and Antitumoral Evaluation of C-6 Alkyl and Alkenyl Side Chain Pyrimidine Derivatives

Krištafor, Svjetlana; Gazivoda Kraljević, Tatjana; Makuc, Damjan; Plavec, Janez; Šuman, Lidija; Kralj, Marijeta; Raić-Malić, Silvana (2009) Synthesis, Structural Studies and Antitumoral Evaluation of C-6 Alkyl and Alkenyl Side Chain Pyrimidine Derivatives. Molecules, 14 (12). pp. 4866-4879. ISSN 1420-3049

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Official URL: https://doi.org/10.3390/molecules14124866

Abstract

The synthetic route for introduction of fluorophenylalkyl (compounds 5, 7, 14 and 15) and fluorophenylalkenyl (compounds 4E and 13) side chains at C-6 of the pyrimidine nucleus involved the lithiation of the pyrimidine derivatives 1, 2 and 11 and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with 2-fluorophenylacetone, 4-fluoroacetophenone or ethyl 4-fluorobenzoate as electrophiles. The structures of novel compounds were confirmed by 1H , 19F- and 13C-NMR and MS. Compounds 8 and 10 containing unsaturated fluorophenylalkyl side chains showed better inhibitory effect than their saturated fluorophenylalkylated pyrimidine counterparts 7 and 9. A conformational study based on NOE enhancements showed the importance of the double bond and substitution in the side chain for the conformational preferences in relation to inhibitory activity. Among all tested compounds, C-5 furyl (12) and phenyl (13 and 15) substituted pyrimidine derivatives showed significant cytostatic activities against all tested tumor cell lines.

Item Type:

Article

Uncontrolled Keywords:

C-6 alkyl and alkenyl pyrimidine derivatives ; NMR conformational analysis ; cytostatic activity evaluation

Subjects:

NATURAL SCIENCES > Chemistry

Divisions:

Division of Molecular Medicine

Projects:

Project title	Project leader	Project code	Project type
Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA-	Marijeta Kralj	098-0982464-2514	MZOS
Razvoj i primjena novih molekula u pozitron-emisijskoj tomografiji (PET)-	Silvana Raić-Malić	125-0982464-2925	MZOS

Depositing User:

Marijeta Kralj

Date Deposited:

24 Feb 2020 15:22

URI:

http://fulir.irb.hr/id/eprint/5311

DOI:

10.3390/molecules14124866