摘要
追溯到19世纪60年代,Melville Wolfrom的无环糖的合成,核苷酸类似物合成的灵活性已经成为了比较感兴趣的领域。然而,这种概念违背了多年的酶底物结合理论。 直到阿昔洛韦和替诺福韦的发现及其随后的FDA批准,抗病毒药物设计中的无环方法论才得以发展。最近发现,活泼性核苷能够克服耐药性重新引起了大家对核苷药物设计领域的兴趣。对下一代活泼核苷的的焦点将会从糖部分转移至碱基部分。碱基易变性领域已经得到了较大发展,如类似物Seley-Radtke“灵活复合物”和Herdewijn的C5替代的2’-deoxyuridines。最近,关于无环糖这些方法论的结合已经产生了一系列拥有多种抗病毒性质的无环活泼碱基核苷,其中一些为首次显示出抗冠状病毒活性。本文对许多活泼核苷与他们相应的核酸碱基做了对比。
关键词: 无环的,抗病毒,药物设计,耐药性,易变,核苷
Current Medicinal Chemistry
Title:Flexibility as a Strategy in Nucleoside Antiviral Drug Design
Volume: 22 Issue: 34
Author(s): H. L. Peters, T. C. Ku and K. L. Seley-Radtke
Affiliation:
关键词: 无环的,抗病毒,药物设计,耐药性,易变,核苷
摘要: As far back as Melville Wolfrom's acyclic sugar synthesis in the 1960's, synthesis of flexible nucleoside analogues have been an area of interest. This concept, however, went against years of enzyme-substrate binding theory. Hence, acyclic methodology in antiviral drug design did not take off until the discovery and subsequent FDA approval of such analogues as Acyclovir and Tenofovir. More recently, the observation that flexible nucleosides could overcome drug resistance spawned a renewed interest in the field of nucleoside drug design. The next generation of flexible nucleosides shifted the focus from the sugar moiety to the nucleobase. With analogues such as Seley-Radtke "fleximers", and Herdewijn's C5 substituted 2’-deoxyuridines, the area of base flexibility has seen great expansion. More recently, the marriage of these methodologies with acyclic sugars has resulted in a series of acyclic flex-base nucleosides with a wide range of antiviral properties, including some of the first to exhibit anti-coronavirus activity. Various flexible nucleosides and their corresponding nucleobases will be compared in this review.
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Cite this article as:
H. L. Peters, T. C. Ku and K. L. Seley-Radtke , Flexibility as a Strategy in Nucleoside Antiviral Drug Design, Current Medicinal Chemistry 2015; 22 (34) . https://dx.doi.org/10.2174/0929867322666150818103624
DOI https://dx.doi.org/10.2174/0929867322666150818103624 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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