Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity
The synthesis of the products of the 1,3-propanesultone ring opening during its interaction with amides of pyridinecarboxylic acids has been carried out. The dependence of the yield of the reaction products on the position (<i>ortho</i>-, <i>meta</i>-, <i>para</i>...
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/21/7542 |
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| author | Eugene P. Kramarova Sophia S. Borisevich Edward M. Khamitov Alexander A. Korlyukov Pavel V. Dorovatovskii Anastasia D. Shagina Konstantin S. Mineev Dmitri V. Tarasenko Roman A. Novikov Alexey A. Lagunin Ivan Boldyrev Aiarpi A. Ezdoglian Natalia Yu. Karpechenko Tatiana A. Shmigol Yuri I. Baukov Vadim V. Negrebetsky |
| author_facet | Eugene P. Kramarova Sophia S. Borisevich Edward M. Khamitov Alexander A. Korlyukov Pavel V. Dorovatovskii Anastasia D. Shagina Konstantin S. Mineev Dmitri V. Tarasenko Roman A. Novikov Alexey A. Lagunin Ivan Boldyrev Aiarpi A. Ezdoglian Natalia Yu. Karpechenko Tatiana A. Shmigol Yuri I. Baukov Vadim V. Negrebetsky |
| author_sort | Eugene P. Kramarova |
| collection | DOAJ |
| description | The synthesis of the products of the 1,3-propanesultone ring opening during its interaction with amides of pyridinecarboxylic acids has been carried out. The dependence of the yield of the reaction products on the position (<i>ortho</i>-, <i>meta</i>-, <i>para</i>-) of the substituent in the heteroaromatic fragment and temperature condition was revealed. In contrast to the <i>meta</i>- and <i>para</i>-substituted substrates, the reaction involving <i>ortho</i>-derivatives at the boiling point of methanol unexpectedly led to the formation of a salt. On the basis of spectroscopic, X-Ray, and quantum-chemical calculation data, a model of the transition-state, as well as a mechanism for this alkylation reaction of pyridine carboxamides with sultone were proposed in order to explain the higher yields obtained with the nicotinamide and its <i>N</i>-methyl analog compared to <i>ortho</i> or <i>meta</i> parents. Based on the analysis of ESP maps, the positions of the binding sites of reagents with a potential complexing agent in space were determined. The in silico evaluation of possible biological activity showed that the synthetized compounds revealed some promising pharmacological effects and low acute toxicity. |
| first_indexed | 2024-03-09T18:47:36Z |
| format | Article |
| id | doaj.art-080c465885b4411f8fc49211e013f536 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:47:36Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-080c465885b4411f8fc49211e013f5362023-11-24T06:05:58ZengMDPI AGMolecules1420-30492022-11-012721754210.3390/molecules27217542Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological ActivityEugene P. Kramarova0Sophia S. Borisevich1Edward M. Khamitov2Alexander A. Korlyukov3Pavel V. Dorovatovskii4Anastasia D. Shagina5Konstantin S. Mineev6Dmitri V. Tarasenko7Roman A. Novikov8Alexey A. Lagunin9Ivan Boldyrev10Aiarpi A. Ezdoglian11Natalia Yu. Karpechenko12Tatiana A. Shmigol13Yuri I. Baukov14Vadim V. Negrebetsky15Department of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaLaboratory of Physical Chemistry, Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 450071 Ufa, RussiaLaboratory of Physical Chemistry, Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 450071 Ufa, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaNational Research Center “Kurchatov Institute”, 123098 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaN.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaDepartment of Medical Chemistry and Toxicology, Pirogov National Research Medical University, Ministry of Health of Russia, 117997 Moscow, RussiaThe synthesis of the products of the 1,3-propanesultone ring opening during its interaction with amides of pyridinecarboxylic acids has been carried out. The dependence of the yield of the reaction products on the position (<i>ortho</i>-, <i>meta</i>-, <i>para</i>-) of the substituent in the heteroaromatic fragment and temperature condition was revealed. In contrast to the <i>meta</i>- and <i>para</i>-substituted substrates, the reaction involving <i>ortho</i>-derivatives at the boiling point of methanol unexpectedly led to the formation of a salt. On the basis of spectroscopic, X-Ray, and quantum-chemical calculation data, a model of the transition-state, as well as a mechanism for this alkylation reaction of pyridine carboxamides with sultone were proposed in order to explain the higher yields obtained with the nicotinamide and its <i>N</i>-methyl analog compared to <i>ortho</i> or <i>meta</i> parents. Based on the analysis of ESP maps, the positions of the binding sites of reagents with a potential complexing agent in space were determined. The in silico evaluation of possible biological activity showed that the synthetized compounds revealed some promising pharmacological effects and low acute toxicity.https://www.mdpi.com/1420-3049/27/21/7542derivatives of pyridine carboxylic acidssulfobetainesmechanism of reactionNMR and FT-IR spectroscopyX-rayquantum-chemical calculations |
| spellingShingle | Eugene P. Kramarova Sophia S. Borisevich Edward M. Khamitov Alexander A. Korlyukov Pavel V. Dorovatovskii Anastasia D. Shagina Konstantin S. Mineev Dmitri V. Tarasenko Roman A. Novikov Alexey A. Lagunin Ivan Boldyrev Aiarpi A. Ezdoglian Natalia Yu. Karpechenko Tatiana A. Shmigol Yuri I. Baukov Vadim V. Negrebetsky Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity Molecules derivatives of pyridine carboxylic acids sulfobetaines mechanism of reaction NMR and FT-IR spectroscopy X-ray quantum-chemical calculations |
| title | Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity |
| title_full | Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity |
| title_fullStr | Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity |
| title_full_unstemmed | Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity |
| title_short | Pyridine Carboxamides Based on Sulfobetaines: Design, Reactivity, and Biological Activity |
| title_sort | pyridine carboxamides based on sulfobetaines design reactivity and biological activity |
| topic | derivatives of pyridine carboxylic acids sulfobetaines mechanism of reaction NMR and FT-IR spectroscopy X-ray quantum-chemical calculations |
| url | https://www.mdpi.com/1420-3049/27/21/7542 |
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