Biopolym. Cell. 2002; 18(3):237-242.
Bioorganic Chemistry
New 6-azauracil derivatives – amides of as-triazine carbon acids: their synthesis and antimicrobial activity
1Alexeeva I. V., 1Palchikovskaya L. I., 2Harchenko S. N., 2Baschta E. V., 1Platonov M. O., 1Kostina V. G., 1Usenko L. S., 1Lysenko N. A., 2Malko V. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. National Agrarian University UAAN
    15, Heroyev Oborony Str., Kyiv, Ukraine, 03041

Abstract

Three series of new 6- azauracil derivatives, differing by structural motives of the spacer linking a heterocycle with carbamide fragments have been synthesized and researched on the basic principles of bioisosterism concept. The antimicrobial activity of these new compounds has been detected in test-cultures of bacteria, micelial and yeast-like fungi. The results obtained indicate that the 6-azauracil-5-propanic and 5-thioacetic acid derivatives can be modified to enhance significantly their antibacterial potency.

References

[1] Patani GA, LaVoie EJ. Bioisosterism: a rational approach in drug design. Chem Rev. 1996;96(8):3147-3176.
[2] Preobrazhenskaya MH, Mel'nik SYa. Analogs components of nucleic acids - inhibitors of nucleic acid metabolism. Itogi nauki i tekhniki (Ser. Bioorg. khimiya; vol 1). 1984; 59-70
[3] ?koda J. Mechanism of Action and Application of Azapyrimidines. Prog Nucleic Acid Res Mol Biol. 1963;197–219.
[4] Pesticide Manual. Eds. NN Melnikov, KV Novozhylov, CR Belan et al. M.: Khimia, 1985; 352 p.
[5] Pat. BDR N 2138031., CA. Herbicidal as-triazin-5-ones. W. Draber, K. Diskore, H. Timmer. Publ. 1978.
[6] Nalepa K, Bekarek V, Slouka J. Reaction of some derivatives of 1,2,4-triazine with organomagnesium halides, hydrogen peroxide and thiocreosol. J Pract Chem. 1972; 314(5-6):477-8.
[7] Bennett GB, Mason RB, Alden LJ, Roach JB Jr. Synthesis and antiinflammatory activity of trisubstituted pyrimidines and triazines. J Med Chem. 1978;21(7):623-8.
[8] Pat. USA N 4636508. 5-Pyrimidine-carboxyamides and treatment of leukemia therewith. A. D. Brewer, J. A. Minatelli. Publ. 1987.
[9] Ognyanik SS, Tarnavsky SS, Sikora LI, Alekseeva IV. Synthesis and spectroscopic study of 3-thio-6-alkylaminosubstituted 1,2,4-triazines-5. Ukr Khim Zh. 1988;54(11):1197-9.
[10] Bobek M, Farka? J, Gut J. Nucleic acids components and their analogues. XCI. An improved synthesis of 6-azauracil and its 5-substituted derivatives. Coll Czech Chem Commun. 1967;32(3):1295–8.
[11] Cristescu C, Marcus J. Derivate des 3,5 dihydro. l,2,4. triazins (6-azauracils) mit mutmabticher cytostatischer Wirkung (I). Pharmazie. 1961; 16: 135-137.
[12] Weygand-Hilgetag. Organish-chemische experimetierkunst. Verlag. Leipzig, 1964.
[13] Cristescu C. as-triazine derivatives with potential therapeutic action. X. 6-Carboxyhydrazide-as-triazines. Rev roum. chim. 1970; 15(9): 1409-14.
[14] The chemistry heterocyclic compounds. Ed. H. Neunhoeffer, P. Willey. New York: Chichester Intersci., 1973. Vol. 33. 1075 p.
[15] Taylor EC, Martin SF. Synthesis of some 7-aryl-6-azapteridines from 1,2,4-triazine intermediates. J Org Chem. 1972;37(24):3958–60.
[16] Alekseeva IV, Shalamaj AS, Turov AV, Chernetskij VP. 5-amino substituted N-methyl-6-azauracils. Ukr Khim Zh. 1978;43(10):1064-9.
[17] Vilai VI. Experimental mycology. Kiev: Naukova Dumka, 1982. 395 p.
[18] Kharchenko SI, Litvin VP, Tarabara IN. Handbook of fungal infections and Mycotoxicoses farm animals. Kiev: Urozhay, 1982;168 p.