Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides
Heterocyclic compounds remain the most promising group of compounds, through which the new drugs with characteristic list of properties are successfully created. Examples of this systems are 1,2,4-triazole and pyrazole. The presence in one molecule structure of fragments of two different azaheterocy...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Zaporizhzhia State Medical and Pharmaceutical University
2019-03-01
|
| Series: | Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki |
| Subjects: | |
| Online Access: | http://pharmed.zsmu.edu.ua/article/view/158913/158772 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849686535248543744 |
|---|---|
| author | A. S. Hotsulia S. O. Fedotov |
| author_facet | A. S. Hotsulia S. O. Fedotov |
| author_sort | A. S. Hotsulia |
| collection | DOAJ |
| description | Heterocyclic compounds remain the most promising group of compounds, through which the new drugs with characteristic list of properties are successfully created. Examples of this systems are 1,2,4-triazole and pyrazole. The presence in one molecule structure of fragments of two different azaheterocycles is synthetically interesting and allows increasing the probability to obtain biologically active substance with a wide spectrum of action.The aim of the work was to optimize the synthesis conditions and investigate the properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides in case of change of chemical process conditions.Methods and results. Ethyl 5-methyl-1H-pyrazole-3-carboxylate, which was obtained by known techniques using acetone, diethyl oxalate, sodium methoxide, followed by hydrazine hydrate in equivalent amount, was used as the key starting reagent. The resulting ethyl 5-methyl-1H-pyrazole-3-carboxylate was used to carry out hydrazinolysis reactions and nucleophilic addition of phenyl isothiocyanate with subsequent alkaline heterocyclicization. The synthesized 5-(5-methyl-1H-pyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiole was used in alkylation reactions with promising reagents for the design of pharmacophoric fragments. The products of such reaction are N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides. The structure of the resulting compounds was confirmed by elemental analysis, 1H NMR spectroscopy, IR spectrophotometry. The individuality of the substances was determined by thin-layer chromatography and chromatographic mass spectrometry. For synthesized compounds, preliminary screening was performed using the PASS On-line® software and molecular docking.Conclusions. N-R-2-5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides are obtained with high yields and purity, their properties are investigated. |
| format | Article |
| id | doaj-art-fa6f89339c6c44068a327a536efc817c |
| institution | DOAJ |
| issn | 2306-8094 2409-2932 |
| language | English |
| publishDate | 2019-03-01 |
| publisher | Zaporizhzhia State Medical and Pharmaceutical University |
| record_format | Article |
| series | Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki |
| spelling | doaj-art-fa6f89339c6c44068a327a536efc817c2025-08-20T03:22:39ZengZaporizhzhia State Medical and Pharmaceutical UniversityAktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki2306-80942409-29322019-03-012114910.14739/2409-2932.2019.1.158913Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamidesA. S. HotsuliaS. O. FedotovHeterocyclic compounds remain the most promising group of compounds, through which the new drugs with characteristic list of properties are successfully created. Examples of this systems are 1,2,4-triazole and pyrazole. The presence in one molecule structure of fragments of two different azaheterocycles is synthetically interesting and allows increasing the probability to obtain biologically active substance with a wide spectrum of action.The aim of the work was to optimize the synthesis conditions and investigate the properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides in case of change of chemical process conditions.Methods and results. Ethyl 5-methyl-1H-pyrazole-3-carboxylate, which was obtained by known techniques using acetone, diethyl oxalate, sodium methoxide, followed by hydrazine hydrate in equivalent amount, was used as the key starting reagent. The resulting ethyl 5-methyl-1H-pyrazole-3-carboxylate was used to carry out hydrazinolysis reactions and nucleophilic addition of phenyl isothiocyanate with subsequent alkaline heterocyclicization. The synthesized 5-(5-methyl-1H-pyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiole was used in alkylation reactions with promising reagents for the design of pharmacophoric fragments. The products of such reaction are N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides. The structure of the resulting compounds was confirmed by elemental analysis, 1H NMR spectroscopy, IR spectrophotometry. The individuality of the substances was determined by thin-layer chromatography and chromatographic mass spectrometry. For synthesized compounds, preliminary screening was performed using the PASS On-line® software and molecular docking.Conclusions. N-R-2-5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides are obtained with high yields and purity, their properties are investigated.http://pharmed.zsmu.edu.ua/article/view/158913/158772124-triazolepyrazolephysical-chemical propertiesmolecular docking |
| spellingShingle | A. S. Hotsulia S. O. Fedotov Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki 1 2 4-triazole pyrazole physical-chemical properties molecular docking |
| title | Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides |
| title_full | Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides |
| title_fullStr | Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides |
| title_full_unstemmed | Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides |
| title_short | Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides |
| title_sort | synthesis structure and properties of n r 2 5 5 methyl 1h pyrazole 3 yl 4 phenyl 4h 1 2 4 triazole 3 ylthio acetamides |
| topic | 1 2 4-triazole pyrazole physical-chemical properties molecular docking |
| url | http://pharmed.zsmu.edu.ua/article/view/158913/158772 |
| work_keys_str_mv | AT ashotsulia synthesisstructureandpropertiesofnr255methyl1hpyrazole3yl4phenyl4h124triazole3ylthioacetamides AT sofedotov synthesisstructureandpropertiesofnr255methyl1hpyrazole3yl4phenyl4h124triazole3ylthioacetamides |