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基于氮杂吲哚骨架的潜在抗病毒药物的研发及其未来展望。

Development of Azaindole-Based Frameworks as Potential Antiviral Agents and Their Future Perspectives.

作者信息

Senthil Kumar J B, Das Parthasarathi, Tandon Vibha

机构信息

Drug Discovery Laboratory, Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110 067, India.

Department of Chemistry, University of Delhi, New Delhi 110007, India.

出版信息

J Med Chem. 2022 May 12;65(9):6454-6495. doi: 10.1021/acs.jmedchem.2c00444. Epub 2022 Apr 28.

Abstract

The azaindole (AI) framework continues to play a significant role in the design of new antiviral agents. Modulating the position and isosteric replacement of the nitrogen atom of AI analogs notably influences the intrinsic physicochemical properties of lead compounds. The intra- and intermolecular interactions of AI derivatives with host receptors or viral proteins can also be fine tuned by carefully placing the nitrogen atom in the heterocyclic core. This wide-ranging perspective article focuses on AIs that have considerable utility in drug discovery programs against RNA viruses. The inhibition of influenza A, human immunodeficiency, respiratory syncytial, neurotropic alpha, dengue, ebola, and hepatitis C viruses by AI analogs is extensively reviewed to assess their plausible future potential in antiviral drug discovery. The binding interaction of AIs with the target protein is examined to derive a structural basis for designing new antiviral agents.

摘要

氮杂吲哚(AI)骨架在新型抗病毒药物的设计中持续发挥着重要作用。调节AI类似物中氮原子的位置和等电子取代基会显著影响先导化合物的内在物理化学性质。通过在杂环核心中精心放置氮原子,还可以微调AI衍生物与宿主受体或病毒蛋白的分子内和分子间相互作用。这篇综述文章广泛探讨了在针对RNA病毒的药物发现计划中具有重要应用价值的AI。文章广泛综述了AI类似物对甲型流感病毒、人类免疫缺陷病毒、呼吸道合胞病毒、嗜神经性α病毒、登革热病毒、埃博拉病毒和丙型肝炎病毒的抑制作用,以评估它们在抗病毒药物发现中未来可能的潜力。研究了AI与靶蛋白的结合相互作用,以推导设计新型抗病毒药物的结构基础。

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