1-(2-deoxy-2,2-difluoro-α-D-erythropentofuranosyl)uracil

• 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-(2-deoxy-2,2-difluoro-α-D-erythropentofuranosyl)uracil
• 英文别名: 2'-Deoxy-2',2'-difluoro-a-uridine；1-[(2S,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• 化学式: C₉H₁₀F₂N₂O₅
• 分子量: 264.186
• InChiKey: FIRDBEQIJQERSE-QXRNQMCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  [(2R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,3-difluorooxolan-2-yl] methanesulfonate 生成 1-(2-deoxy-2,2-difluoro-α-D-erythropentofuranosyl)uracil
  参考文献：
  名称：

  HERTEL, LARRY W.

  摘要：

  DOI：

文献信息

• Anti-HCV nucleoside derivatives
  申请人：——

  公开号：US20030008841A1

  公开（公告）日：2003-01-09

  The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

  本发明涉及新颖和已知的嘌呤和嘧啶核苷衍生物，已发现这些衍生物对丙型肝炎病毒（HCV）具有活性。本发明声明利用这些衍生物治疗HCV感染，以及本文所披露的新颖核苷衍生物。
• Degradation Chemistry of Gemcitabine Hydrochloride, a New Antitumor Agent
  作者：Sally L. Anliker、Michael S. McClure、Thomas C. Britton、Erwin A. Stephan、Steven R. Maple、Gary G. Cooke

  DOI：10.1002/jps.2600830524

  日期：1994.5

  The anti-tumor agent gemcitabine hydrochloride, a beta-difluoronucleoside, is remarkably stable in the solid state. In 0.1 N HCI solution at 40 degrees C, deamination of gemcitabine occurs, yielding its uridine analogue. Approximately 86% of the initial gemcitabine remains after 4 weeks under these conditions. Cleavage of the N-glycosidic bond of gemcitabine or conversion to its alpha-anomer in 0.1

  抗肿瘤剂吉西他滨盐酸盐，β-二氟核苷，在固态下非常稳定。在40°C的0.1 N HCl溶液中，吉西他滨发生脱氨基反应，得到其尿苷类似物。在这些条件下4周后，约有86％的初始吉西他滨残留。在4周内未观察到吉西他滨的N-糖苷键断裂或在0.1 N HCl溶液中转化为其α-端基异构体。但是，这项工作表明，吉西他滨盐酸盐在40°C的0.1 N NaOH中会发生异构化。在所用的碱性条件下，经过4周后，仍有约72％的初始吉西他滨存在。在这些条件下也会形成尿苷水解产物。在基本条件下不常见的反化反应，通过NMR和质谱法对色谱分离的α-端基异构体进行表征，已经证实了这一点。提出了涉及无环中间体的机理。
• HERTEL, LARRY W.
  作者：HERTEL, LARRY W.

  DOI：——

  日期：——
• NUCLEOSIDE DERIVATIVES FOR THE TREATMENT OF HEPATITIS C
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1315736A2

  公开（公告）日：2003-06-04
• [EN] NUCLEOSIDE DERIVATIVES<br/>[FR] DERIVES DE NUCLEOSIDES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2002018404A2

  公开（公告）日：2002-03-07

  Use of compounds of formula (I), wherein R1 is hydrogen, hydroxy, alkyl, hydroxyalkyl, alkoxy, halogen, cyano, isocyano or azido; R2 is hydrogen, hydroxy, alkoxy, chlorine, bromine or iodine; R3 is hydrogen; or R?2 and R3¿ together represent =CH¿2?; or R?2 and R3¿ represent fluorine; X is O, s or CH¿2?; a, b, c, d denoting asymmetric carbon atoms each of which is substituted with 4 different substituents; and B signifies a purine base B1 which is connected through the 9-nitrogen of formula (B1), wherein R?4¿ is hydrogen, hydroxyl, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen or SH; R5 is hydrogen, hydroxy, alkyl, haloalkyl, cycloalkyl, alkoxy, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8¿ or SH; R6 is hydrogen, hydroxy, alkyl, alkoxy, alkylthio, aryloxy, arylthio, heterocyclyl, NR7R8, halogen, SH or cyano; R?7 and R8¿ are independently of each other hydrogen, alkyl, aryl, hydroxyalkyl, alkenylalkyl, alkynylalkyl, cycloalkyl or acyl; R9 is hydrogen, alkyl or aryl; or B signifies an oxidised purine base B2 which is connected through the 9-nitrogen of formula (B2), wherein R?4, R5 and R6¿ are as defined above; or B signifies a purine base B3 which is connected through the 9-nitrogen of formula (B3), wherein R?4 and R6¿ are as defined above; R10 is hydrogen, alkyl or aryl; Y is O, S or NR11; R11 is hydrogen, hydroxy, alkyl, OR9, heterocyclyl or NR?7R8; R7, R8 and R9¿ are as defined above; or B signifies a pyrimidine base B4 which is connected through the 1-nitrogen of formula (B4), wherein Z is O or S; R12 is hydrogen, hydroxy, alkyl, alkoxy, haloalkyl, alkylthio, aryl, aryloxy, arylthio, heterocyclyl, heterocyclylamino, halogen, NR?7R8, NHOR9, NHNR7R8¿ or SH; R13 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl or halogen; R?7, R8 and R9¿ are as defined above; or B signifies a pyrimidine base B5 which is connected through the 1-nitrogen of formula (B5), wherein Y, Z, R10 are as defined above for the treatment of diseases mediated by the Hepatitis C Virus (HIV) or for the preparation of a medicament for such treatment. The invention is concerned with novel and known purine and pyrimidine nucleoside derivatives, their use as inhibitors of subgenomic Hepatitis C Virus (HCV) RNA replication and pharmaceutical compositions of such compounds.