Synthesis and anаlgеsic activity 5-methyl-3-aryl[1,2,4]triazolo[4,3-a]pyrimidin-7-oles derivatives

  • A. G. Ogorodnik Shevchenko Chernihiv National Pedagogical University
  • V. A. Yanchenko Shevchenko Chernihiv National Pedagogical University
  • L. S. Bobkova SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
  • N. M. Seredinska SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
  • A. M. Demchenko SI «Institute of pharmacology and toxicology of NAMS of Ukraine», Kyiv
Keywords: 5-methyl-3-aryl[1,2,4]triazolo[4,3-a]pyrimidin-7-oles, ketorolac, the anаlgеsic activity

Abstract

Pain is a signal of inflammation and disruption of the body. It is the most important protective and adaptive mechanism that ensuring the safety of the individual. A strong and prolonged effect of "pain" irritant arising in injuries or after surgical manipulation transforms the protective reaction of the body to harmful factor that is the cause of secondary violations physiological processes.

The aim of this work was the synthesis of substances in a series of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidine-7-ol and study the analgesic effect of the synthesized compounds.

The objects of our research were selected derivatives of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidine-7-ol, which were synthesized by condensation and subsequent cyclization of 6-methyl-2-metylsulfanilpirymidyn-4-ol (1) with the corresponding substituted benzoic acid hydrazide The primary evaluation of analgesic activity conducted on thermal  stimulation models («hot plate»).

A number of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol derivatives were synthesized, and their structure and purity were confirmed by 1H NMR spectroscopy. The analgesic activity of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol was investigated in order to reveal the structure-activity relationship.

The screening for analgesic activity for 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol derivatives in in vivo experiments on hot plate models showed that the highest activity Was noted for the compound containing the methyl group in the fourth position of the aryl substituent, which is 184.28% of the change in the latent period of the reaction, which exceeds the action of the reference preparation of ketorolac by 71.57%. The introduction of halogens into the aryl moiety leads to a decrease in the analgesic activity of the compounds.

A series of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidine-7-ol derivatives were synthesized by condensation and subsequent cyclization of 6-methyl-2-metylsulfanylpirymydyn-4-ol with relevant substituted hydrazide of benzoic acid. The structure and purity of obtained compounds were confirmed by 1H NMR spectroscopy. The analgesic activity of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pyrimidin-7-ol was investigated in order to reveal the structure-activity relationship.

The screening of analgesic activity of 5-methyl-3-aryl [1,2,4] triazolo [4,3-a] pirymidyn-7-ol derivatives in vivo models for «hot plate» shows that the highest activity was noted for compound containing methyl group in the fourth position of the aryl substituent, which is 184.28% change latent period reaction, that exceeds effect reference drug ketorolac at 71.57%. The introduction of halogens in the aryl fragment leads to a decrease analgesic activity of compounds.

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Published
2018-08-14
How to Cite
Ogorodnik, A. G., Yanchenko, V. A., Bobkova, L. S., Seredinska, N. M., & Demchenko, A. M. (2018). Synthesis and anаlgеsic activity 5-methyl-3-aryl[1,2,4]triazolo[4,3-a]pyrimidin-7-oles derivatives. Farmatsevtychnyi Zhurnal, (2), 55-61. https://doi.org/10.32352/0367-3057.2.17.07
Section
Synthesis and analysis of biologically active compounds