In this work, hydrazides, salicylidenehydrazones and 1,2,4-triazoles (2-methyl-1H-benzimidazol-1-yl)ethanoic and (5,6-dimethyl-1H-benzimidazol-1-yl)ethanoic acids were synthesized and studied. It was shown that standard methods for the synthesis of hydrazides, acylhydrazones and triazoles are also applicable to benzimidazole derivatives. The conversion of hydrazides to salicylidene hydrazones and 1,2,4-triazoles leads to an increase in the stability of the compounds, since. Storing hydrazides of these acids in air leads to their slow oxidation. A prediction was made of the potential biological activity of the synthesized hydrazides, salicylidenehydrazones and 1,2,4-triazoles using the PASSOnline Internet service. In the series of compounds hydrazide – salicylidehydrazone and 1,2,4-triazole for (2-methyl-1H-benzimidazol-1-yl)ethanoic acid the calculated Pa value was 0.625 – 0.757 – 0.258, respectively. For (5,6-dimethyl-1H-benzimidazol-1-yl)ethanoic acid the calculated Pa value was 0.641 – 0.405, respectively. 1,2,4-Triazole does not have this activity. Using the PASSOnline program, it was shown that when moving from (2-methyl-1H-benzimidazol-1-yl)ethanoic acid hydrazide to (5,6-dimethyl-1H-benzimidazol-1-yl)ethanoic acid hydrazide, a slight increase in anti-tuberculosis activity is observed (Pa = 0.625 and 0.641). For the corresponding salicylidene hydrazones, an inverse dependence of this type of activity was observed. 1,2,4-Triazoles practically do not exhibit this type of biological activity, which is due to the blocking of the active hydrazide group. The composition and structures of the starting and synthesized compounds were confirmed by elemental analysis, PMR and IR spectroscopy.
benzimidazole, hydrazide, acylhydrazone, salicylidenehydrazone, 1,2,4-triazole, biological activity, anti-tuberculosis activity, PASSOnline
1. Shah K. Benzimidazole: a promising pharmacophore / K. Shah, S. Chhabra, S. K. Shrivastava, P. Mishra // Med. Chem. Res. – 2013. – Vol. 22, № 11. – P. 5077–5104.
2. Ajani O. O. Functionalized Benzimidazole Scaffolds: Privileged Heterocycle for Drug Design in Therapeutic Medicine / O. O. Ajani, D. V.Aderohunmu, C. O. Ikpo, A. E. Adedapo, I. O.Olanrewaju // Arch. Pharm.
3. Rubcov M. V. Sinteticheskie himiko-farmacevticheskie preparaty / M. V. Rubcov, A. G. Baychikov. – M.: Medicina, 1971. – 328 s.
4. Mashkovskiy D. M. Lekarstvennye sredstva. Izd. 16. / D. M. Mashkovskiy. – M.: Novaya volna, 2020. – 1216 c.
5. Vekariya N. A. Synthesis of isoxazoles and quinoxalines as potential anticancer agents / N. A. Vekariya // Indian Journal of Chemistry. – 2003. – Vol. 42B. – R. 421–424.
6. Soni L. K. Anti-microbial benzimidazole derivatives: synthesis and in vitro biological evaluation / L. K. Soni, T. Narsinghani, A. Sethi // Med. Chem. Res. – 2012. – Vol. 21. – № 12. – P. 4330–4334.
7. Spasov A. A. Antiserotoninovaya aktivnost' proizvodnyh triciklicheskih benzimidazol'nyh sistem / A. A. Spasov, M. V. Chernikov, D. S.Yakovlev//Him.-farmac. zhurnal.– 2006.–T. 40, № 11.– S.23–26.
8. Pozharskiy A. F. Sintez N-alkilbenzimidazolov / A. F. Pozharskiy, A. M. Simonov // Zhurn. org. him. – 1963. – T. 33. – S. 179–181.
9. Soundararajan R. Regioselective N-alkylation of benzimidazole via an organotin route / R. Soundararajan, T. Balasubramanian // Tetrahedron Lett. – 1984. – Vol. 25, № 48. – P. 5555–5558.
10. Schukina M. N. Aromaticheskie izonikotinoilgidrazony – novyy klass himioterapevticheskih protivotuberkuleznyh veschestv / M. N. Schukina, G. N. Pershin, E. D. Sazonova, O. O. Makeeva // Problemy
11. Poroykov V. V. Komp'yuternyy prognoz biologicheskoy aktivnosti himicheskih soedineniy kak osnova dlya poiska i optimizacii bazovyh struktur novyh lekarstv / V. V. Poroykov, D. A. Filimonov
12. Pharma expert predictive services «PASSOnline» [Electronic resource]: FSBI «Research Institute of biomedical chemistry named after V. N. Orekhovich» The Russian Academy of medical Sciences. –
13. Ioffe B. V. Himiya organicheskih proizvodnyh gidrazina / B. V. Ioffe, M. A. Kuznecov, A. A. Potehin. – L.: Himiya, 1979. – 224 s.
14. Potts K. T. The Chemistry of 1,2,4-Triazoles / K. T. Potts // Chem. Rev. 1961. – Vol. 61. – P. 87–127.
15. Sil'versteyn R. Spektrometricheskaya identifikaciya organicheskih soedineniy: ucheb. posobie / R. Sil'versteyn, G. Bassler, T. Moril. – M.: Mir, 1977. – S. 125–215.
