(2S)methyl 2-((((2R,3R,4R,5R) 5(2-amino-6-(azetidin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate | 1064685-09-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)methyl 2-((((2R,3R,4R,5R) 5(2-amino-6-(azetidin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate
• 英文别名: (S)-2-{[(2R,3R,4R,5R)-5-(2-amino-6-azetidin-1-yl-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-ylmethoxy]phenoxy-phosphorylamino}propionic acid methyl ester；methyl (2S)-2-[[[(2R,3R,4R,5R)-5-[2-amino-6-(azetidin-1-yl)purin-9-yl]-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1064685-09-1
• 化学式: C₂₄H₃₁FN₇O₇P
• 分子量: 579.525
• InChiKey: DUEOCJDMECUWFS-HEOQURLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  176
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (2S)methyl 2-((((2R,3R,4R,5R) 5(2-amino-6-(azetidin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate 在 水 、 三乙胺 作用下， 反应 20.0h， 以80%的产率得到(2S)-2-((((2R,3R,4R,5R)-5-(2-amino-6-(azetidin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphorylamino)propanoic acid
  参考文献：
  名称：

  [EN] NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS
  [FR] ANALOGUES DE NUCLÉOSIDE

  摘要：

  公开号：

  WO2010075517A3
• 作为产物：
  描述：

  6-氯-9-[(2R)-3,5-二-O-苯甲酰基-2-脱氧-2-氟-2-甲基-beta-D-赤式五呋喃糖基]-9H-嘌呤-2-胺 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 生成 (2S)methyl 2-((((2R,3R,4R,5R) 5(2-amino-6-(azetidin-1-yl)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate
  参考文献：
  名称：

  Discovery of PSI-353661, a Novel Purine Nucleotide Prodrug for the Treatment of HCV Infection

  摘要：

  Hepatitis C virus afflicts approximately 180 million people worldwide, and the development of direct acting antivirals may offer substantial benefit compared to the current standard of care. Accordingly, prodrugs of 2'-deoxy-2'-fluoro-2'-C-methylguanosine monophosphate analogues were prepared and evaluated for their anti-HCV efficacy and tolerability. These prodrugs demonstrated >1000 fold greater potency than the parent nucleoside in a cell based replicon assay as a result of higher intracellular triphosphate levels. Further optimization led to the discovery of the clinical candidate PSI-353661, which has demonstrated strong in vitro, inhibition against HCV without cytotoxicity and equipotent activity against both the wild type and the known S282T nucleoside/tide resistant replicon. PSI-353661 is currently in preclinical development for the treatment of HCV.

  DOI：

  10.1021/ml100209f

文献信息

• NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS
  申请人：SOFIA MICHAEL JOSEPH

  公开号：US20100016251A1

  公开（公告）日：2010-01-21

  Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

  本文披露了用于治疗哺乳动物病毒感染的核苷类衍生物的磷酰胺酯前药，该前药是一种化合物，其立体异构体、盐（酸性或碱性加合盐）、水合物、溶剂合物或结晶形式，由以下结构表示：同时还披露了治疗方法、用途和制备过程，每种方法均利用由式I表示的化合物。
• NUCLEOSIDE ANALOGS
  申请人：BAO DONGHUI

  公开号：US20100286083A1

  公开（公告）日：2010-11-11

  A purified compound having activity against hepatitis C virus is disclosed.

  本发明揭示了一种对丙型肝炎病毒具有活性的纯化化合物。
• SYNTHESIS OF PURINE NUCLEOSIDES
  申请人：Chun Byoung-Kwon

  公开号：US20120316327A1

  公开（公告）日：2012-12-13

  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过程，该过程涉及一种化合物及其立体异构体、盐（酸性或碱性加合盐）、水合物、溶剂合物或其晶体形式。
• NUCLEOSIDE PHOSPHORAMIDATES
  申请人：SOFIA MICHAEL JOSEPH

  公开号：US20110015146A1

  公开（公告）日：2011-01-20

  A nucleoside compound having activity against hepatitis C virus is disclosed.

  本发明揭示了一种具有抗丙型肝炎病毒活性的核苷化合物。
• 3',5'-cyclic nucleoside phosphate analogues
  申请人：Gilead Pharmasset LLC

  公开号：EP2671888A1

  公开（公告）日：2013-12-11

  A compound or salt thereof having the following structure useful for the treatment of hepatitis C virus (HCV): wherein R7 is C1-6 alkyl or C3-6 cycloalkyl and R8 is -O(C1-6 alkyl) or -O(C3-6 cycloalkyl).

  具有以下结构的化合物或其盐，可用于治疗丙型肝炎病毒（HCV）： 其中 R7 为 C1-6 烷基或 C3-6 环烷基，R8 为 -O(C1-6烷基)或 -O(C3-6环烷基)。