氟化核苷:合成、构象调节和治疗应用

Shantanu Pal, Girish Chandra, Samridhi Patel, Sakshi Singh
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引用次数: 11

摘要

在过去的二十年中,核苷氟化已成为最有前途的工具,用于获得生物活性化合物,可以通过影响药效学和药代动力学特性来维持临床试验。由于氟固有的独特性质和其明智地引入到分子中,使得相应的核苷代谢非常稳定,亲脂性,并打开了分子间结合的新位点。对各种核苷的氟化已经进行了广泛的研究,因此,一系列的氟化核苷被用于不同的治疗用途,这些用途要么被FDA批准,要么处于临床试验的后期阶段。本文综述了核苷氟化化学的最新进展,包括碳环核苷、无环核苷和构象偏向核苷等新型类似物的产生及其生物学特性、氟对构象、寡核苷酸稳定性的影响及其在治疗中的应用。
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Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application
Over the last twenty years, fluorination on nucleoside has established itself as the most promising tool to use to get biologically active compounds that could sustain the clinical trial by affecting the pharmacodynamics and pharmacokinetic properties. Due to fluorine's inherent unique properties and its judicious introduction into the molecule, makes the corresponding nucleoside metabolically very stable, lipophilic, and opens a new site of intermolecular binding. Fluorination on various nucleosides has been extensively studied as a result, a series of fluorinated nucleosides come up for different therapeutic uses which are either approved by the FDA or under the advanced stage of the clinical trial. Here in this review, we are summarizing the latest development in the chemistry of fluorination on nucleoside that led to varieties of new analogs like carbocyclic, acyclic, and conformationally biased nucleoside and their biological properties, the influence of fluorine on conformation, oligonucleotide stability, and their use in therapeutics.
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