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Molecules 2009, 14(12), 4866-4879; doi:10.3390/molecules14124866
Article

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

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Received: 30 September 2009; in revised form: 19 November 2009 / Accepted: 25 November 2009 / Published: 27 November 2009
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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.
Keywords: C-6 alkyl and alkenyl pyrimidine derivatives; NMR conformational analysis; cytostatic activity evaluations C-6 alkyl and alkenyl pyrimidine derivatives; NMR conformational analysis; cytostatic activity evaluations
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Krištafor, S.; Gazivoda Kraljević, T.; Makuc, D.; Plavec, J.; Šuman, L.; Kralj, M.; Raić-Malić, S. Synthesis, Structural Studies and Antitumoral Evaluation of C-6 Alkyl and Alkenyl Side Chain Pyrimidine Derivatives S. Molecules 2009, 14, 4866-4879.

AMA Style

Krištafor S, Gazivoda Kraljević T, Makuc D, Plavec J, Šuman L, Kralj M, Raić-Malić S. Synthesis, Structural Studies and Antitumoral Evaluation of C-6 Alkyl and Alkenyl Side Chain Pyrimidine Derivatives S. Molecules. 2009; 14(12):4866-4879.

Chicago/Turabian Style

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 S." Molecules 14, no. 12: 4866-4879.


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