6-ethoxy-9-((2S,4aR,6R,7R,7aR)-7-fluoro-2-isopropoxy-7-methyl-2-oxo-tetrahydro-2λ(5)-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl)-9H-purin-2-ylamine | 1199809-77-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-ethoxy-9-((2S,4aR,6R,7R,7aR)-7-fluoro-2-isopropoxy-7-methyl-2-oxo-tetrahydro-2λ(5)-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl)-9H-purin-2-ylamine
• 英文别名: (2S,4aR,6R,7R,7aR)-6-(2-amino-6-ethoxy-9H-purin-9-yl)-7-fluoro-2-isopropoxy-7-methyltetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinine 2-oxide；6-ethoxy-9-((2S,4aR,6R,7R,7aR)-7-fluoro-2-isopropoxy-7-methyl-2-oxohexahydro-2,5-furo[3,2d][1,3,2]dioxaphosphinin-6-yl)-9H-purine-2-ylamine；Guanosine, 2'-deoxy-6-O-ethyl-2'-fluoro-2'-methyl-, cyclic 3',5'-(1-methylethyl (R)-phosphate), (2'R)-；9-[(2S,4aR,6R,7R,7aR)-7-fluoro-7-methyl-2-oxo-2-propan-2-yloxy-4,4a,6,7a-tetrahydrofuro[3,2-d][1,3,2]dioxaphosphinin-6-yl]-6-ethoxypurin-2-amine
• CAS: 1199809-77-2
• 化学式: C₁₆H₂₃FN₅O₆P
• 分子量: 431.361
• InChiKey: PVRFQJIRERYGTQ-DSQUMVBZSA-N

物化性质

• 沸点：
  622.5±65.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  isopropyl phosphorodichloridate 、 (2R,3R,4R,5R)-5-(2-amino-6-ethoxy-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-ol 在 三乙胺 、 N-甲基咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 0.84h， 生成 6-ethoxy-9-((2S,4aR,6R,7R,7aR)-7-fluoro-2-isopropoxy-7-methyl-2-oxo-tetrahydro-2λ(5)-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl)-9H-purin-2-ylamine
  参考文献：
  名称：

  [EN] CYCLIC NUCLEOSIDE DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS NUCLÉOSIDES CYCLIQUES ET UTILISATIONS CORRESPONDANTES

  摘要：

  提供了一种具有化学式（I）的化合物，已被证明对治疗由病毒感染引起的疾病有用，其中R1、R2和R3如本文所定义。

  公开号：

  WO2014082935A1

文献信息

• プリンヌクレオシドの合成
  申请人：ギリアド ファーマセット エルエルシー

  公开号：JP2015227337A

  公开（公告）日：2015-12-17

  PROBLEM TO BE SOLVED: To provide compounds useful for treating conditions caused by viral factors.SOLUTION: The present invention provides compounds represented by formula (I) or formula (II) or salts thereof, and methods of synthesizing the same. (R1 is phenyl group or the like; R2 is H or the like; R3a and R3b are each independently H, a C1-10 alkyl group, or the like; R4 is H, a C1-10 alkyl group, a C3-10 cycloalkyl group, or the like; R5 is H or the like; R6 is H, CH3, or the like; R7 is H, an n-alkyl group, a cycloalkyl group, or the like; R8 is O (lower alkyl), O (lower cycloalkyl), or the like; and R9 is an NH2 group or the like.)

  要解决的问题：提供用于治疗由病毒因素引起的疾病的化合物。解决方案：本发明提供由式（I）或式（II）代表的化合物或其盐，以及它们的合成方法。（其中，R1是苯基或类似物；R2是H或类似物；R3a和R3b分别独立地是H、C1-10烷基或类似物；R4是H、C1-10烷基、C3-10环烷基或类似物；R5是H或类似物；R6是H、CH3或类似物；R7是H、n-烷基、环烷基或类似物；R8是O（较低烷基）、O（较低环烷基）或类似物；R9是NH2基团或类似物。）
• 2′-Deoxy-2′-α-fluoro-2′-β-C-methyl 3′,5′-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: Discovery of PSI-352938
  作者：P. Ganapati Reddy、Donghui Bao、Wonsuk Chang、Byoung-Kwon Chun、Jinfa Du、Dhanapalan Nagarathnam、Suguna Rachakonda、Bruce S. Ross、Hai-Ren Zhang、Shalini Bansal、Christine L. Espiritu、Meg Keilman、Angela M. Lam、Congrong Niu、Holly Micolochick Steuer、Phillip A. Furman、Michael J. Otto、Michael J. Sofia

  DOI：10.1016/j.bmcl.2010.10.035

  日期：2010.12

  A series of novel 2′-deoxy-2′-α-fluoro-2′-β-C-methyl 3′,5′-cyclic phosphate nucleotide prodrug analogs were synthesized and evaluated for their in vitro anti-HCV activity and safety. These prodrugs demonstrated a 10–100-fold greater potency than the parent nucleoside in a cell-based replicon assay due to higher cellular triphosphate levels. Our structure–activity relationship (SAR) studies provided

  合成了一系列新型 2'-deoxy-2'-α-fluoro-2'-β- C-甲基 3',5'-环状磷酸核苷酸前药类似物，并对其体外抗 HCV 活性和安全性进行了评估。由于更高的细胞三磷酸盐水平，这些前药在基于细胞的复制子测定中显示出比母体核苷高 10-100 倍的效力。我们的构效关系 (SAR) 研究提供了在大鼠口服给药时在大鼠肝脏中产生高水平活性三磷酸盐的化合物。这些研究最终导致了临床开发候选者24a (PSI-352938) 的选择。
• SYNTHESIS OF PURINE NUCLEOSIDES
  申请人：CHUN BYOUNG-KWON

  公开号：US20100279973A1

  公开（公告）日：2010-11-04

  A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.

  一种制备核苷衍生物的磷酰胺酯前药或环磷酸酯前药的方法，该方法涉及一种化合物及其立体异构体、盐（酸性或碱性加成盐）、水合物、溶剂化合物或其晶体形式。
• NUCLEOSIDE CYCLICPHOSPHATES
  申请人：DU Jinfa

  公开号：US20100081628A1

  公开（公告）日：2010-04-01

  Cyclic phosphate of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof, represented by the following structure:

  环状核苷衍生物的磷酸酯，用于治疗哺乳动物中的病毒感染，该化合物及其立体异构体、盐（酸性或碱性加成盐）、水合物、溶剂化合物或其结晶形式，由以下结构表示：
• CYCLIC NUCLEUOSIDE DERIVATIVES AND USES THEREOF
  申请人：LIAO Lv

  公开号：US20140205566A1

  公开（公告）日：2014-07-24

  A compound of Formula (I) is provided that has been shown to be useful for treating a disease caused by a viral infection: wherein R 1 , R 2 and R 3 are as defined herein.

  提供了一种化合物(I)的公式，已被证明对治疗由病毒感染引起的疾病有用：其中R1、R2和R3的定义如本文所述。