SYNTHESIS OF TIOSOLFOESTERS WITH S-TRIAZINE FRAGMENT

2018;
: 98-104
1
Department of Technology of Biologically Active Substances, Pharmacy & Biotechnology, Lviv National Polytechnic University
2
Lviv Polytechnic National University
3
Department of Technology of Biologically Active Substances, Pharmacy & Biotechnology, Lviv National Polytechnic University
4
Lviv Polytechnic National University
5
Lviv Polytechnic National University

Cyanuric chloride is a valuable starting agent for the direct obtaining of highly structured molecules. The substitution of chlorine atoms in the molecule of cyanuric chloride by various pharmacophores’ fragments provides the obtaining a number of 1,3,5-triazine derivatives, among which the promising biologically active substances showing antimicrobial, anticancer, antimalarial and antiviral activity were detected.

Derivatives of thiosulfonic acids are very interesting because thiosulfoesters are structural analogues of natural antibacterial substances. It is known that synthetic esters of thiosulfoacids possess the biological activity, which often exceeds the efficiency of natural analogues. Most of them are offered as medicines, preservatives of fruit and vegetables, effective remedies for plant protection, growth regulators, biocidal additives, insecticides and radioprotector. In addition, esters of thiosulfoacid are effective sulfenilating and sulfonylating reagents in organic synthesis, and valuable objects for solving complex issues of molecular biology and biochemistry.

Taking into account the wide range of possible practical applications of both thiosulphoesters and 1,3,5-triazines, this work proposes the ways of combining these "preferred structures" in one molecule, since this opens up prospects for the search for new biologically active compounds (biocides, fungicides, pesticides, medicinal substances).

The interaction of 2,4,6-trichloro-1,3,5-triazine with potassium and sodium salts of aromatic thiosulfonic acids under different temperature conditions was determined. It has been shown that this interaction occurs with the formation of products of mono- and di-substitution of chlorine atoms of cyanuric chloride in various ratios in all investigated cases.

 The new objects (4,6-dichloro-1,3,5-triazine thiosulfonester, 6-chloro-1,3,5-triazine and isocyanuric dithiosulfoester) were added to the combinatorial library of thiosulfoesters with the sim-triazine fragment for the further search the biologically active compounds Structure and characteristics of synthesized compounds have been confirmed by IR, 1H NMR spectroscopy, elemental analysis and by TLC.

1. Mooibroek T. J. The s-triazine ring, a remarkable unit to generate supramolecular interactions / Mooibroek T. J., Gamez P. // Inorg. Chim. Acta. – 2007. – Vol. 360(1). – P. 381–404.

2. Mylari B. L. Design and synthesis of a novel family of triazine-based inhibitors of sorbitol dehydrogenase with oral activity: 1-{4-[3R, 5S-dimethyl-4-(4methyl-[1, 3, 5] triazin-2-yl)-piperazin-1-yl]-[1, 3, 5] triazin-2-yl}-(R) ethanol / Mylari B. L., Withbroe G. J., Beebe D. A., Brackett N. S., Conn E. L., Coutcher J. B. et al. // Biorg. Med. Chem. – 2003. – Vol. 11(19). – P. 4179–4188.

3. Henke B. R. A new series of estrogen receptor modulators that display selectivity for estrogen receptor β / Henke B. R., Consler T. G., Go N., Hale R. L., Hohman D. R., Jones S. A. et al. // J. Med. Chem. – 2002. – Vol. 45(25). – P. 5492–5505. 
4. Desai N. Synthesis and study of 1, 3, 5-tria- zine based thiazole derivatives as antimicrobial agents / Desai N., Makwana A. H., Rajpara K. // J. Saudi. Chem. Soc. – 2016. – Vol. 20. – P. S334–S341.
5. Vembu S. Potential antibacterial activity of triazine dendrimer: synthesis and controllable drug release properties / Vembu S. Pazhamalai S., Gopalakrishnan M. // Biorg. Med. Chem. – 2015. – Vol. 23(15). – P. 4561–4566.

6. Patel A. B. An efcient synthesis of new thiazolidin-4-one fused s-triazines as potential antimicrobial and antican- cer agents // Patel A. B., Chikhalia K. H., Kumari P. // J Saudi Chem Soc.– 2014. – Vol. 18(5). – P. 646–656.

7. Maeda M. Antimetastatic and antitumor efects of 2, 4-diamino-6-(pyridine-4-yl)-1, 3, 5-triazine (4PyDAT) on the high lung metastatic colon 26 tumor in mice / Maeda M., Ligo M., Tsuda H., Fujita H., Yonemura Y., Nakagawa K. et al. // Anticancer Drug Des. – 2000. – Vol. 15(3). – P. 217–223.

8. Baindur N. 2-Hydroxy-4, 6-diamino-[1, 3, 5] triazines: a novel class of VEGF-R2 (KDR) tyrosine kinase inhibitors /Baindur N., Chadha N., Brandt B. M., Asgari D., Patch R. J., Schalk-HiHi C. et al. // J. Med. Chem. – 2005. – Vol. 48(6). – P.1717–1720.

9. Jensen N. P. Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. // Jensen N. P.,  Ager A. L., Bliss R. A., Canfeld C. J., Kotecka B. M., Rieckmann K. H. et al. // J. Med. Chem. – 2001. –
Vol. 44(23). –P. 3925–3931.

10. Agarwal A. Syntheses of 2, 4, 6-trisubstituted triazines as antimalarial agents / Agarwal A., Srivastava K., Puri S., Chauhan P. M. // Biorg. Med. Chem. Lett. – 2005. – Vol. 15(3). – P. 531–533.

11. Renka Yu. V. Sintez solyanokislih soley pohIdnih 2-pIrolIdin-4-anIlIno- 6-arilamIno-1,3,5-triazinu I doslIdzhennya Yih aktivnostI schodo rinovIrusu shtamu HGP na klItinah HELA OHIO-1 / Yu. V. Renka, V. A. SIriy // Ukrainica Bioorganica Acta. – 2012. – Vol. 1. – P. 61–67.
12. V. Lubenets, S. Vasylyuk, N. Monka, Kh. Bolibrukh, O. Komarovska-porokhnyavets, D. Baranovych, R. Musyanovych, E. Zaczynska, A. Czarny, U. Nawrot, V. Novikov. Synthesis and antimicrobial properties of 4-acylaminobenzenethiosulfoacid S-esters // Saudi Pharmaceutical Journal. – 2017. – Vol. 25, No. 2. – P. 266–274.

13. Trost B. M. Alpha-Sulphenylated Carbonyl Compounds in Organic Synthesis // Trost B. M. // Chem. Rev. – 1978. – No. 78. – Р. 363.

14. Afonso C. A. M. Synthesis of 2,4,6-trisubstituted-1,3,5-triazines / C. A. M. Afonso, N. M. T. Lourenco, A. Rosatella // Molecules. – 2006. – Vol. 11. – P. 81–102.

15. Vasyilyuk S. V. Vzaimodeystvie tsianurhlorida s alkantiosulfonatami / S. V. Vasyilyuk, V. I. Lubenets, Yu. I. Byichko, V. P. Novikov // HGS. – 2008. – # 1. – S. 132–133.

16. Monka N. Ya. Prognozovaniy skrinIng bIologIchnoYi aktivnostI azotovmIsnih geterotsiklIchnih esterIv alIfatichnih tIosulfokislot / Monka N. Ya., HomItskiy D. O., Shiyan G. B., Vasilyuk S. V., Baranovich D. B., Lubenets V. I., NovIkov V. P. // VIsnik Nats. un-tu “LvIvska polItehnIka” „HImIya, tehnologIya rechovin ta Yih zastosuvannya”. – LvIv. – 2010. – # 667. – S. 182–187.

17. Vasylyuk S. Modification of alkyl esters of 4-aminobenzenethiosulfonic acid by s-triazine fragment and investigation of their growth-regulative activity / Vasylyuk S., Komarovska-Porokhnyavets O., Novikov V., Lubenets V. //
Chemistry and Chemical Technology. – 2018. – Vol. 12 (1). – P. 24–28.

18. Kelarev V. I. Sintez 2,4-diamino-sim-triazinov, soderzhaschih fragmentyi prostranstvenno zatrudnennogo fenola / V. I. Kelarev, A. S. Remizov, R. A. Karahanov [i dr.] // HGS. – 1992. – # 10. – S. 1395–1399.

19. Kelarev V. I. Sintez i svoystva proizvodnyih sim-triazina. Vzaimodeystvie 2-alkil-4,6-bis (trihlormetil)-sim-triazinov, soderzhaschih vyisshie alkilnyie radikalyi, s ammiakom i alifaticheskimi  minami / V. I. Kelarev, Ammar Dibi, A. F. Lunin // HGS. – 1985. – # 11. – S. 1557– 1561.

20. Fizicheskie metodyi v himii geterotsiklicheskih soedineniy / pod red. A. R. Katritskogo. – M.: Himiya,1968. – 594 c.