Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives

Q3 Pharmacology, Toxicology and Pharmaceutics
D. Yakovlev, P. Vassiliev, Ya. V. Agatsarskaya, A. A. Brigadirova, K. T. Sultanova, M. Skripka, A. Spasov, K. Savateev, V. Rusinov, D. Maltsev
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引用次数: 1

Abstract

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.
偶氮[1,5-a]嘧啶硝基衍生物中腺苷A1受体的新型拮抗剂Searching
引言:腺苷A1Rs配体是开发治疗阵发性室上性心动过速、心绞痛、高甘油三酯血症、2型糖尿病、神经性疼痛和心力衰竭的药物的潜在候选者。同时,缺乏能够调节A1受体功能的药物。许多A1拮抗剂处于临床试验的不同阶段;其他药物的选择性不是很强,或者其治疗作用的广度不够。因此,在四唑并[1,5-a]嘧啶的硝基衍生物和1,2,4-三唑并[1,5-a]嘧啶 具有科学意义。材料与方法:采用体外和体外两种方法对活性化合物进行了筛选。在第一阶段,使用Microcosm BioS软件对A1拮抗活性进行计算机预测。在第二阶段,在离体小鼠心房模型中验证了预测结果。结果和讨论:基于与标准物最大相似性方法的预测结果,选择了最具活性的化合物III、VIII和XVII。通过离体心房法检测预测结果,化合物VIII在10μmol/L浓度下具有A1阻断作用。结论:筛选出最有前景的A1阻断化合物;它是四唑并[1,5-a]嘧啶的衍生物,代码为VIII。对其药理性质的进一步深入研究具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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