Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives
Introduction: Ligands of adenosine A1Rs are potential candidates for the development of drugs for the treatment of paroxysmal supraventricular tachycardia, angina pectoris, hypertriglyceridemia, type 2 diabetes mellitus, neuropathic pain, and heart failure. At the same time, there is a deficiency of...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Belgorod National Research University
2022-06-01
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| Series: | Research Results in Pharmacology |
| Online Access: | https://rrpharmacology.ru/article/77854/download/pdf/ |
| _version_ | 1797422307890692096 |
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| author | Dmitry S. Yakovlev Pavel M. Vassiliev Yana V. Agatsarskaya Anastasia A. Brigadirova Kira T. Sultanova Maria O. Skripka Alexander A. Spasov Konstantin V. Savateev Vladimir L. Rusinov Dmitriy V. Maltsev |
| author_facet | Dmitry S. Yakovlev Pavel M. Vassiliev Yana V. Agatsarskaya Anastasia A. Brigadirova Kira T. Sultanova Maria O. Skripka Alexander A. Spasov Konstantin V. Savateev Vladimir L. Rusinov Dmitriy V. Maltsev |
| author_sort | Dmitry S. Yakovlev |
| collection | DOAJ |
| description | Introduction: Ligands of adenosine A1Rs are potential candidates for the development of drugs for the treatment of paroxysmal supraventricular tachycardia, angina pectoris, hypertriglyceridemia, type 2 diabetes mellitus, neuropathic pain, and heart failure. At the same time, there is a deficiency of drugs that can regulate the functions of A1 receptors. A number of A1-antagonists are at the various stages of clinical trials; other drugs are not very selective or are characterized by an insufficient breadth of their therapeutic action. Therefore, the search for new medicinal compounds for the prevention and treatment of A1-depended diseases among nitro derivatives of tetrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine is of scientific interest. Materials and methods: The search for active compounds was carried out by in silico and in vitro methods. At the first stage, a computer forecast of A1-antagonistic activity was carried out using the Microcosm BioS software. At the second stage, the prediction results were verified in vitro in a model of isolated mouse atria. Results and discussion: Based on the results of the prediction by the method of maximum similarity to standards, the most active compounds III, VIII, and XVII were selected. After testing the prediction results by the isolated atria method, the compound VIII was characterized by A1-blocking effect in vitro at a concentration of 10 μmol/L. Conclusion: The most promising compound with A1-blocking effect in vitro was identified; it is a derivative of tetrazolo[1,5-a]pyrimidine under the code of VIII. It is of interest for us for further in-depth study of its pharmacological properties. |
| first_indexed | 2024-03-09T07:30:19Z |
| format | Article |
| id | doaj.art-7924b960ea9043d3a35444ae2f8b4398 |
| institution | Directory Open Access Journal |
| issn | 2658-381X |
| language | English |
| last_indexed | 2024-03-09T07:30:19Z |
| publishDate | 2022-06-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj.art-7924b960ea9043d3a35444ae2f8b43982023-12-03T06:24:11ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2022-06-0182697510.3897/rrpharmacology.8.7785477854Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivativesDmitry S. Yakovlev0Pavel M. Vassiliev1Yana V. Agatsarskaya2Anastasia A. Brigadirova3Kira T. Sultanova4Maria O. Skripka5Alexander A. Spasov6Konstantin V. Savateev7Vladimir L. Rusinov8Dmitriy V. Maltsev9Volgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityUral Federal UniversityUral Federal UniversityVolgograd Medical Research CenterIntroduction: Ligands of adenosine A1Rs are potential candidates for the development of drugs for the treatment of paroxysmal supraventricular tachycardia, angina pectoris, hypertriglyceridemia, type 2 diabetes mellitus, neuropathic pain, and heart failure. At the same time, there is a deficiency of drugs that can regulate the functions of A1 receptors. A number of A1-antagonists are at the various stages of clinical trials; other drugs are not very selective or are characterized by an insufficient breadth of their therapeutic action. Therefore, the search for new medicinal compounds for the prevention and treatment of A1-depended diseases among nitro derivatives of tetrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine is of scientific interest. Materials and methods: The search for active compounds was carried out by in silico and in vitro methods. At the first stage, a computer forecast of A1-antagonistic activity was carried out using the Microcosm BioS software. At the second stage, the prediction results were verified in vitro in a model of isolated mouse atria. Results and discussion: Based on the results of the prediction by the method of maximum similarity to standards, the most active compounds III, VIII, and XVII were selected. After testing the prediction results by the isolated atria method, the compound VIII was characterized by A1-blocking effect in vitro at a concentration of 10 μmol/L. Conclusion: The most promising compound with A1-blocking effect in vitro was identified; it is a derivative of tetrazolo[1,5-a]pyrimidine under the code of VIII. It is of interest for us for further in-depth study of its pharmacological properties.https://rrpharmacology.ru/article/77854/download/pdf/ |
| spellingShingle | Dmitry S. Yakovlev Pavel M. Vassiliev Yana V. Agatsarskaya Anastasia A. Brigadirova Kira T. Sultanova Maria O. Skripka Alexander A. Spasov Konstantin V. Savateev Vladimir L. Rusinov Dmitriy V. Maltsev Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives Research Results in Pharmacology |
| title | Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives |
| title_full | Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives |
| title_fullStr | Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives |
| title_full_unstemmed | Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives |
| title_short | Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives |
| title_sort | searching for novel antagonists of adenosine a1 receptors among azolo 1 5 a pyrimidine nitro derivatives |
| url | https://rrpharmacology.ru/article/77854/download/pdf/ |
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