摘要
背景:腺苷是一种内源性嘌呤核苷,介导多种重要的生物学过程和疾病,如血管扩张、炎症、癌症、伤口愈合、缺血再灌注损伤、帕金森病、感染性疾病等中枢神经系统疾病。尤其重要的是A2A受体在肺、肝脏、心血管组织、白细胞、中性粒细胞和内皮细胞中的表达。本文综述了2005-2017年开发的最新A2A受体激动剂及其对其他腺苷受体的选择性及其潜在的治疗应用。方法:从最常见的文献数据库中广泛检索A2A受体激动剂及其在炎症、哮喘和慢性阻塞性肺疾病、心肌灌注显像、脓毒症、类风湿关节炎和伤口愈合等方面的最新研究成果。结果:近十年来,为开发腺苷受体激动剂和拮抗剂来治疗多种疾病做出了巨大的努力。因此,对于A2A受体激动剂已经发现130多篇论文和评论,其中许多强调了这些化合物在该领域的有用性。结论:虽然到目前为止,许多A2A受体激动剂由于其副作用而在临床试验中失败,但其中一些已被批准用于保护心脏缺血-再灌注损伤和贫血。最近报道的人A2A受体与激动剂UK-432097配合物的晶体结构是开发具有新的治疗应用价值的新型选择性A2A配体的基础。
关键词: 腺苷,A2A腺苷受体,激动剂,结构-活性关系,炎症,治疗应用。
Current Medicinal Chemistry
Title:A2A Adenosine Receptor Agonists and their Potential Therapeutic Applications. An Update
Volume: 25 Issue: 30
关键词: 腺苷,A2A腺苷受体,激动剂,结构-活性关系,炎症,治疗应用。
摘要: Background: Adenosine is an endogenous purine nucleoside, which mediates a variety of important biological processes and diseases, such as vasodilation, inflammation, cancer, wound healing, ischemia reperfusion injury, Parkinson disease, infectious diseases, and other CNS disorders. Particularly important are the A2A receptors that have been expressed in the lung, liver, heart, cardiovascular tissues, leukocytes, neutrophils, and endothelial cells. This review provides an update of the latest A2A receptor agonists developed in the period 2005-2017, their selectivity regarding other adenosine receptors and their potential therapeutic applications.
Methods: I have conducted an extensive search from the most common bibliographic databases for critically review the most recent works on the A2A receptor agonists and their therapeutic applications in inflammation, asthma and chronic obstructive pulmonary disease, myocardial perfusion imaging, sepsis, rheumatoid arthritis, and wound healing, among others.
Results: In the last decade, a great deal of effort has been devoted to develop adenosine receptor agonists and antagonists for treatment of a number of diseases. Thus, for A2A receptor agonists more than 130 papers and reviews have been found, many of them highlighting the usefulness of these compounds in the field.
Conclusions: Although so far many of the A2A receptor agonists have failed in clinical trials due to their side effects, some of them have been approved for protection against cardiac ischemia-reperfusion injury and anemia. The recently reported crystal structure of the human A2A receptor in complex with the agonist UK-432097 is a fundamental keystone for the development of new and selective A2A ligands with new therapeutic applications.
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A2A Adenosine Receptor Agonists and their Potential Therapeutic Applications. An Update, Current Medicinal Chemistry 2018; 25 (30) . https://dx.doi.org/10.2174/0929867325666180313110254
DOI https://dx.doi.org/10.2174/0929867325666180313110254 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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