Assessment of Antihypoxic Activity of S-analoges of Dihydropyrimidin-2-ones and Their Condensed Derivatives

N. Buzmakova, T. M. Zamaraeva, D. Ivkin, D. Apushkin, N. V. Slepova, N. V. Dozmorova
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Abstract

Introduction. Antioxydant activity, membrane stabilizing and cytoprotective effect of dihydropyrimidin analoges are widely described in various literary sources. One of the importantant mechanisms of action of antioxidants is their antihypoxic activity. It is the ability to increase tissue resistance to hypoxia. The search for drugs to increase the body's resistance under hypoxic conditions is an actual task in experimental and clinical pharmacology.Aim. Study of the antihypoxic activity of new S-analogs of dihydropyrimidin-2-ones and their condensed derivatives in various models of hypoxia.Materials and methods. 13 compounds S-analogs of dihydropyrimidin-2-ones and their condensed derivatives are objects of research. Their structure has been confirmed by spectroscopy methods. The antihypoxic activity was carried out by recommended methods for preclinical study of new pharmacological substances.Results and discussion. This paper presents the results of testing the obtained compounds of different structures on three models of hypoxia. The activity of a number of condensed tricyclic derivatives of dihydropyrimidine-2-thiones was studied in more detail using a model of acute normobaric hypoxia with hypercapnia.Conclusion. The compounds did not demonstrate high antihypoxic activity; some «structure-property» patterns were revealed.
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二氢嘧啶-2-酮的 S-类似物及其缩合衍生物的抗缺氧活性评估
导言。二氢嘧啶类似物的抗氧化活性、膜稳定和细胞保护作用在各种文献资料中都有广泛的描述。抗氧化剂的重要作用机制之一是其抗缺氧活性。它能够增强组织对缺氧的抵抗力。寻找在缺氧条件下增强机体抵抗力的药物是实验和临床药理学的一项实际任务。研究二氢嘧啶-2-酮的新 S-类似物及其缩合衍生物在各种缺氧模型中的抗缺氧活性。研究对象为 13 个二氢嘧啶-2-酮的 S-类似物及其缩合衍生物。它们的结构已通过光谱方法得到确认。抗缺氧活性采用了新药理物质临床前研究的推荐方法。本文介绍了在三种缺氧模型上对所获得的不同结构的化合物进行测试的结果。通过使用急性常压缺氧和高碳酸血症模型,对一些二氢嘧啶-2-硫酮缩合三环衍生物的活性进行了更详细的研究。这些化合物并没有表现出很高的抗缺氧活性,但揭示了一些 "结构-性质 "模式。
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