(2R,3R,4R,5R)-5-(4-Benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-yl benzoate | 1192577-84-6

• 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: (2R,3R,4R,5R)-5-(4-Benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-yl benzoate
• 英文别名: [(2R,3R,4R,5R)-5-(4-benzamido-2-oxopyrimidin-1-yl)-4-fluoro-2-(hydroxymethyl)-4-methyloxolan-3-yl] benzoate
• CAS: 1192577-84-6
• 化学式: C₂₄H₂₂FN₃O₆
• 分子量: 467.454
• InChiKey: DTWACZZPIWZBGO-PDKZGUECSA-N

物化性质

• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  119.75
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-5-(4-Benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-yl benzoate 在 2,6-二甲基吡啶 、 ammonium hydroxide 、 三甲基溴硅烷 、 palladium 10% on activated carbon 、 氢气 、 三氟乙酸吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 73.0h， 生成 (2-((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)ethyl)phosphonic acid
  参考文献：
  名称：

  Evaluation of 2′-α-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase

  摘要：

  Ribonucleoside phosphonate analogues containing 2'-alpha-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase. The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1.9-2.1 mu M, but only modest cell-based activity in the HCV replicon. Pro- drugs of the parent nucleoside phosphonates improved the cell-based activity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.095
• 作为产物：
  描述：

  在 吡啶 、 溶剂黄146 作用下， 反应 66.0h， 生成 (2R,3R,4R,5R)-5-(4-Benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-yl benzoate
  参考文献：
  名称：

  Evaluation of 2′-α-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase

  摘要：

  Ribonucleoside phosphonate analogues containing 2'-alpha-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase. The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1.9-2.1 mu M, but only modest cell-based activity in the HCV replicon. Pro- drugs of the parent nucleoside phosphonates improved the cell-based activity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.095

文献信息

• 一种桥环氟代酯及其制备方法和应用
  申请人：上海泓博智源医药股份有限公司

  公开号：CN107200757B

  公开（公告）日：2020-06-02

  本发明公开了一种全新的桥环氟代酯(1R,4R,5R,6R)‑6‑氟‑6‑甲基‑2,7‑二氧双环[2.2.1]庚基‑5‑甲酸酯(结构式见如V所示)及其制备方法、以及用该化合物V来合成PSI‑6130进而合成索非布韦目的的应用。其结构如下：本发明合成路线简短，立体构型选择性优异而且可控，反应过程不使用重金属、剧毒原料，产生的三废少，环境友好，具有明显的经济效益，适合工业化大生产。
• NUCLEOSIDE PHOSPHONATE DERIVATIVES
  申请人：Or Yat Sun

  公开号：US20090274686A1

  公开（公告）日：2009-11-05

  The present invention discloses compounds of formula (I) or (II), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds.

  本发明揭示了化合物的公式(I)或(II)，或其药学上可接受的盐、酯或前药：这些化合物抑制、预防或治疗异常细胞增殖和/或病毒感染，特别是HIV、HCV或HBV。因此，本发明的化合物干扰病毒的复制周期，同时也可用作抗病毒剂，或干扰宿主细胞的生化过程，同时也可用作抗增殖剂。本发明还涉及包含上述化合物的药物组合物，用于治疗患有病毒感染和/或细胞增殖的受试者。该发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的病毒感染和/或细胞增殖的方法。本发明涉及上述新型抗病毒/抗增殖化合物，包括含有这些化合物的药物组合物，以及用于治疗或预防受试者的病毒感染的方法。