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Pyrimidine and furo[2, 3-d]pyrimidine derivatives: synthesis, cytostatic and antibacterial evaluations

Furo[2, 3-d]pyrimidine are purinomimetics which were subjected to biological investigations to assess their potential therapeutic usefulness. Furopyrimidines attract considerable attention due to their great practical significance through exerting pharmacological potential as antiviral, antimicrobial, and antitumor agents, and is one of the most recently explored scaffolds to have potential anticancer activity through inhibition of various protein kinases.[1] Furthermore, it was found that some 1, 2, 3-triazole tethered pyrimidines and furopyrimidines showed pronounced antiviral and cytostatic activity.[2] In continuation of our efforts towards the fused pyrimidines [3, 4] we prepared C-5 alkynylated pyrimidines and C-6-alkylated furo[2, 3-d]pyrimidines substituted at N-1 or N-3 with butenyl, propargyl and 1, 2, 3-triazolyl substituents. The novel N-substituted and C-5 alkynylated uracil derivatives have been synthesized by N-alkylation of pyrimidine bases and subsequent Pd-catalysed Sonogashira cross-coupling reaction. 1, 2, 3-Triazolyl derivatives were afforded via 'click' reaction and furo[2, 3-d]pyrimidines by in situ O-heteroannulation of C-5 alkynylated derivatives. The novel compounds were evaluated against tumor cell lines (HeLa, CaCo-2, Raji and K562) and on the growth of gram positive and gram negative bacterial strains. References [1] M.A. Aziz, R.A.T. Serya, D.S.Lasheen and K.A.M. Abouzid, Fut. J. Pharm. Scie. 2 (2016) 1-8. [2] I. E. Głowacka, J. Balzarini and A.E. Wróblewski, Eur. J. Med. Chem. 70 (2013) 703–722. [3] T. Gazivoda Kraljević, A. Bistrović, M. Dedić, S. Kraljević Pavelić, M. Sedić and S. Raić-Malić, Tetrahedron Lett. 53 (2012) 5144-5147. [4] T. Gregorić, M. Sedić, P. Grbčić, A. Tomljenović Paravić, S. Kraljević Pavelić, M. Cetina, R. Vianello and S. Raić-Malić, Eur. J. Med. Chem. 125 (2017) 1247-1267.

Pyrimidine, furo[2, 3-d]pyrimidine, click chemistry, Sonogashira cross-coupling reaction, cytostatic evaluations, antibacterial evaluations

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