1-(3,4-dihydroxy-5-(hydroxymethyl)-3-vinyltetrahydrofuran2-yl)pyrimidine-2,4(1H,3H)-dione

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(3,4-dihydroxy-5-(hydroxymethyl)-3-vinyltetrahydrofuran2-yl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-[(2R,3R,4R,5R)-3-ethenyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• 化学式: C₁₁H₁₄N₂O₆
• 分子量: 270.242
• InChiKey: ZOKDDIUZAQJNGA-PNHWDRBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3,4-dihydroxy-5-(hydroxymethyl)-3-vinyltetrahydrofuran2-yl)pyrimidine-2,4(1H,3H)-dione 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 以94%的产率得到1-[(2R,3R,4R,5R)-3-ethyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
  参考文献：
  名称：

  SUBSTITUTED NUCLEOTIDE ANALOGS

  摘要：

  本文披露了磷硫酸酯核苷类似物，合成磷硫酸酯核苷类似物的方法，以及利用磷硫酸酯核苷类似物治疗病毒感染、癌症和/或寄生虫病等疾病和/或症状的方法。

  公开号：

  US20130164261A1
• 作为产物：
  描述：

  [(2R,3R,4R)-3,4,5-tribenzoyloxy-4-ethenyloxolan-2-yl]methyl benzoate 在 甲醇 、 氨 、 四氯化锡 、 牛血清白蛋白 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 1-(3,4-dihydroxy-5-(hydroxymethyl)-3-vinyltetrahydrofuran2-yl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  2′-C-Alkylribonucleosides: Design, Synthesis, and Conformation

  摘要：

  Certain 2'-C-alkylribonucleotides have been designed as potential mechanism-based inactivators of ribonucleotide reductases. A short, flexible route toward the corresponding nucleosides and NMR evidence concerning their preferred solution conformations are discussed.

  DOI：

  10.1080/07328319708006205

文献信息

• Activity of Selected Nucleoside Analogue ProTides against Zika Virus in Human Neural Stem Cells
  作者：Jean A. Bernatchez、Michael Coste、Sungjun Beck、Grace A. Wells、Lucas A. Luna、Alex E. Clark、Zhe Zhu、David Hecht、Jeremy N. Rich、Christal D. Sohl、Byron W. Purse、Jair L. Siqueira-Neto

  DOI：10.3390/v11040365

  日期：——

  an aryloxyl phosphoramidate masking group. Substitution of a 2-(methylthio) ethyl phosphoramidate for the aryloxyl phosphoramidate ProTide group of 2'-C-methyluridine completely abolished antiviral activity of the compound. The aryloxyl phosphoramidate ProTide of 2'-C-methyluridine outperformed the hepatitis C virus (HCV) drug sofosbuvir in suppression of viral titers and protection from cytopathic

  Zika病毒（ZIKV）是一种新兴的黄病毒，可导致胎儿神经发育受损，并与Guillain-Barré综合征有关，由于缺乏针对性的预防或治疗，仍在威胁全球健康。核苷类似物是有效的抗病毒抑制剂的良好实例，使用磷酸掩蔽基团（ProTides）的前药策略已被用于改善核糖核苷类似物的生物利用度。在这里，我们合成并测试了在人类神经干细胞中针对ZIKV的13个ProTides的小型文库。对于具有芳氧基氨基磷酸氨基酯掩蔽基团的2'-C-甲基尿苷和2'-C-乙炔基尿苷脯氨酸，观察到强活性。用2'（甲硫基）氨基磷酸乙酯取代2'的芳氧基氨基磷酸酯ProTide基团 -C-甲基尿苷完全消除了该化合物的抗病毒活性。2'-C-甲基尿苷的芳氧基氨基磷酸氨基甲酸酯ProTide在抑制病毒滴度和防止细胞病变作用方面优于丙型肝炎病毒（HCV）药物sofosbuvir，而随着时间的推移，前者化合物的三磷酸盐活性代谢产物可以更好地与纯化的ZIKV
• SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
  申请人：Alios Biopharma, Inc.

  公开号：EP3421482A1

  公开（公告）日：2019-01-02

  Disclosed herein are nucleotide analogs of formula (I), methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs, wherein the substituents are as defined in the appended claims.

  本文公开了式(I)的核苷酸类似物、合成核苷酸类似物的方法以及用一种或多种核苷酸类似物治疗疾病和/或诸如HCV感染等病症的方法、 其中取代基如所附权利要求中定义。
• 4'-FLUORO-NUCLEOSIDES, 4'-FLUORO-NUCLEOTIDES AND ANALOGS THEREOF FOR THE TREATMENT OF HCV
  申请人：Janssen BioPharma, Inc.

  公开号：EP3912984A1

  公开（公告）日：2021-11-24

  Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.

  本文公开了核苷酸类似物、合成核苷酸类似物的方法以及用一种或多种核苷酸类似物治疗疾病和/或病症（如 HCV 感染）的方法。
• Substituted nucleosides, nucleotides and analogs thereof
  申请人：Janssen BioPharma, Inc.

  公开号：US10780105B2

  公开（公告）日：2020-09-22

  Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.

  本文公开了核苷、核苷酸类似物、合成核苷酸类似物的方法以及用一种或多种核苷和/或核苷酸类似物治疗疾病和/或病症（如丝状病毒感染）的方法。
• A Short, Flexible Route toward 2‘-<i>C</i>-Branched Ribonucleosides
  作者：Rogers E. Harry-O'kuru、Jennifer M. Smith、Michael S. Wolfe

  DOI：10.1021/jo961893+

  日期：1997.3.1

  A five-step synthesis of 2'-C-branched ribonucleosides from commercially obtained 1,3,5-tri-0-benzoyl-alpha-D-ribofuranose (4) is described. The free hydroxyl group of 4 was oxidized in high yield with Dess-Martin periodane reagent. The resultant 2-ketosugar was treated with MeMgBr/TiCl4, CH2=CHMgBr/CeCl3, or TMSC drop CLi/CeCl3, and in each case addition to the ketone proceeded stereoselectively to provide 2-alkylated ribofuranosides. After conversion to the corresponding tetrabenzoyl derivatives, the 2-alkylribofuranosides were coupled to nucleobases under Vorbruggen persilylation conditions, giving the beta-nucleosides with high stereoselectivity. Deprotection with methanolic ammonia provided the title compounds in 17-49% overall yields from 4.