N-[[P(S),2'R]-2'-脱氧-2'-氟-2'-甲基-P-苯基-5'-胞苷酰]-L-丙氨酸异丙酯 | 1334513-10-8

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: N-[[P(S),2'R]-2'-脱氧-2'-氟-2'-甲基-P-苯基-5'-胞苷酰]-L-丙氨酸异丙酯
• 英文名称: isopropyl ((S)-(((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate
• 英文别名: Sofosbuvir impurity J；propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1334513-10-8
• 化学式: C₂₂H₃₀FN₄O₈P
• 分子量: 528.474
• InChiKey: JMTNHBQFZOWQKE-IQWMDFIBSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  10

安全信息

• 储存条件：
  2-8℃

制备方法与用途

Sofosbuvir impurity J 是 sofосbuvir 的非对映异构体，也是其一种杂质。Sofosbuvir（PSI-7977）是一种抑制 HCV RNA 复制的药物，并表现出有效的抗丙型肝炎病毒活性。

反应信息

• 作为反应物：
  描述：

  N-[[P(S),2'R]-2'-脱氧-2'-氟-2'-甲基-P-苯基-5'-胞苷酰]-L-丙氨酸异丙酯 在 硫酸羟胺 作用下， 以 异丙醇 为溶剂， 以68.5%的产率得到
  参考文献：
  名称：

  一种抗冠状病毒的化合物及其制备方法与应用

  摘要：

  本发明涉及一种抗冠状病毒的化合物及其制备方法与应用。本发明的抗冠状病毒的化合物为式I化合物或其药学上可接受的盐，式I化合物具有如下结构：本发明的式I化合物E1、E2、G1、G2对Vero正常细胞的毒性作用很小，但能显著抑制SARS‑CoV‑2病毒对正常细胞的侵染，在细胞水平均对新型冠状病毒SARS‑CoV‑2具有抑制作用，因此本发明的目标化合物具有用于制备抗新型冠状病毒SARS‑CoV‑2药物的潜力。另外，本发明的式I化合物还具有显著的抗MERS‑CoV和SARS‑CoV等冠状病毒的活性，且所测试目标化合物E1、E2、G1、G2较阳性对照药物具有更高的选择性。

  公开号：

  CN113735929A
• 作为产物：
  描述：

  L-丙氨酸异丙酯盐酸盐 在 叔丁基氯化镁 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.68h， 生成 N-[[P(S),2'R]-2'-脱氧-2'-氟-2'-甲基-P-苯基-5'-胞苷酰]-L-丙氨酸异丙酯
  参考文献：
  名称：

  Synthesis of Diastereomerically Pure Nucleotide Phosphoramidates

  摘要：

  Prodrugs of therapeutic nucleoside monophosphates masked as phosphoramidate derivatives have become an increasingly important class of antiviral drugs in pharmaceutical research for delivering nucleotides in vitro and in vivo. Conventionally, phosphoramidate derivatives are prepared as a mixture of two diastereomers. We report a class of stable phosphoramidating reagents containing an amino acid ester and two phenolic groups, one unsubstituted and the other with electron-withdrawing substituents. The reagents can be isolated as single diastereomers and reacted with the 5'-hydroxyl group of nucleosides through selective nucleophilic displacement of the substituted phenol to prepare single diastereomer phosphoramidate products. This method has been used to prepare the HCV clinical candidate PSI-7977 in high yield and high diastereomeric purity.

  DOI：

  10.1021/jo201492m

文献信息

• [EN] 4'-FLUORO-2'-METHYL SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION<br/>[FR] DÉRIVÉS NUCLÉOSIDIQUES À SUBSTITUTION 4'-FLUORO-2'-MÉTHYLE UTILISÉS COMME INHIBITEURS DE LA RÉPLICATION DE L'ARN DU VHC
  申请人：RIBOSCIENCE LLC

  公开号：WO2019060740A1

  公开（公告）日：2019-03-28

  Cytidine nucleoside analogues of Formula I, wherein the variables are as described herein, in combination with uridine nucleoside analogues of Formula II, wherein the variables are as described herein, produce a synergistic effect on the inhibition of HCV polymerase.

  Cytidine核苷类似物的化学式I，其中变量如本文所述，与尿苷核苷类似物的化学式II，其中变量如本文所述，对HCV聚合酶的抑制产生协同作用。
• 4′-fluoro-2′-methyl substituted nucleoside derivatives as inhibitors of HCV RNA replication
  申请人：Riboscience LLC

  公开号：US10682369B2

  公开（公告）日：2020-06-16

  Cytidine nucleoside analogues of Formula I, wherein the variables are as described herein, in combination with uridine nucleoside analogues of Formula II, wherein the variables are as described herein, produce a synergistic effect on the inhibition of HCV polymerase.

  式 I 的胞苷核苷类似物（其中变量如本文所述）与式 II 的尿苷核苷类似物（其中变量如本文所述）的组合、 可产生抑制 HCV 聚合酶的协同效应。
• Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189
  作者：Bryon Simmons、Zhuqing Liu、Artis Klapars、Ana Bellomo、Steven M. Silverman

  DOI：10.1021/acs.orglett.7b00469

  日期：2017.5.5

  A general and efficient method for the synthesis of pronucleotide (ProTide) 5'-phosphoramidate monoesters is :reported. This method consists of a highly stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing, 3'-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.
• 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication
  申请人：Riboscience LLC

  公开号：US20180200280A1

  公开（公告）日：2018-07-19

  Cytidine nucleoside analogues of Formula I, wherein the variables are as described herein, in combination with uridine nucleoside analogues of Formula II, wherein the variables are as described herein, produce a synergistic effect on the inhibition of HCV polymerase.
• 4'-FLUORO-2'-METHYL SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION
  申请人：Riboscience LLC

  公开号：US20190231804A1

  公开（公告）日：2019-08-01

  Cytidine nucleoside analogues of Formula I, wherein the variables are as described herein, in combination with uridine nucleoside analogues of Formula II, wherein the variables are as described herein, produce a synergistic effect on the inhibition of HCV polymerase.