索非布韦代谢物GS-566500 | 1233335-78-8

• 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: 索非布韦代谢物GS-566500
• 中文别名: N-[(2'R)-2'-脱氧-2'-氟-2'-甲基-5'-尿苷酰基]-L-丙氨酸
• 英文名称: (2S)-2-((((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphorylamino)propanoic acid
• 英文别名: L-Alanine, N-((2'R)-2'-deoxy-2'-fluoro-2'-methyl-5'-uridylyl)-；(2S)-2-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-hydroxyphosphoryl]amino]propanoic acid
• CAS: 1233335-78-8
• 化学式: C₁₃H₁₉FN₃O₉P
• 分子量: 411.281
• InChiKey: UOYKQCZOTUPGRY-UARFSYEXSA-N

物化性质

• 密度：
  1?+-.0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（非常轻微，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  175
• 氢给体数：
  5
• 氢受体数：
  11

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  索罗布维	sofosbuvir	1064684-44-1	C22H29FN3O9P	529.459

反应信息

• 作为产物：
  描述：

  索罗布维 在 水 、 三乙胺 作用下， 反应 30.0h， 以92%的产率得到索非布韦代谢物GS-566500
  参考文献：
  名称：

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

  摘要：

  公开号：

  WO2010075517A3

文献信息

• [EN] PHOSPHORAMIDATE NUCLEOSIDE PRODRUG FOR TREATING VIRAL DISEASES AND CANCER, PROCESSES FOR THEIR PREPARATION AND THEIR USE<br/>[FR] PROMÉDICAMENT NUCLÉOSIDE PHOSPHORAMIDATE DESTINÉ AU TRAITEMENT DES MALADIES VIRALES ET DU CANCER, LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION
  申请人：IVACHTCHENKO ALEXANDRE VASILIEVICH

  公开号：WO2018022221A1

  公开（公告）日：2018-02-01

  The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer. The phosphoramidate nucleoside prodrug of the general formula (1), a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, formula (1) wherein: Ar is aryl or hetaryl; R1 is H or CH3, R2 is the substituent selected from OCH2CH=CH2, OCH2CH≡CH, OCH2CH2CH2OCH3, formula (2), formula (3) or formula (4), R3 is H or CH3; R4 is OH, OR5, NR6R7; R5 is C1-C4-alkyl; R6 and R7 are not necessarily the same substituents selected from H or CH3, Z = O, or NH; an arrow (→) indicates the place of substituent connection; Nuc is formula (5) or (6); R8 and R9 are not necessarily the same substituents selected from H, F, Cl, CH3 or OH provided when continuous line and its accompanying dotted line ( ) together are the single carbon-carbon (C-C) bond or R8 and R9 are hydrogen provided when continuous line and its accompanying dotted line ( ) together are the double carbon-carbon bond (C=C); R10 is the substituent selected from R10.1- R10.5; R10.1 R10.2 R10.4 R10.5 ; R11 is the substituent selected from H, F, CI, CH3, or CF3; R12 is hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl; X is oxygen or ethanediyl-1,1 (C=CH2); Y is O, S, CH2, or HO-CH group provided when continuous line and its accompanying dotted line (formula 7) together are the single carbon-carbon (C-C) bond or Y is CH group provided when continuous line and its accompanying dotted line (formula 7) together are the double carbon-carbon bond (C=C), and compound of the general formula (1), stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: Ar is aryl or hetaryl; R1 is H or CH3; R2 is isopropyl; Nuc is formula (8), (9) or (10).

  本发明涉及化疗药物及其用于治疗病毒性和癌症疾病的用途。这些化合物是HCV NS5B聚合酶、HBV DNA聚合酶和HIV-1逆转录酶（RT）抑制剂，用于治疗哺乳动物中的乙型和丙型肝炎感染。这些化合物也对癌症治疗具有兴趣。通用式（1）的磷酰胺核苷前药的立体异构体、同位素富集类似物、药学上可接受的盐、水合物、溶剂合物或晶体或多形式，式（1）其中：Ar为芳基或杂芳基；R1为H或CH3，R2为从OCH2CH=CH2、OCH2CH≡CH、OCH2CH2CH2OCH3、式（2）、式（3）或式（4）中选择的取代基，R3为H或CH3；R4为OH、OR5、NR6R7；R5为C1-C4-烷基；R6和R7不一定相同，选择自H或CH3的取代基，Z=O或NH；箭头（→）表示取代基连接的位置；Nuc为式（5）或（6）；R8和R9不一定相同，选择自H、F、Cl、CH3或OH，提供当连续线及其相应的虚线（）一起为单碳-碳（C-C）键时，或R8和R9为氢，提供当连续线及其相应的虚线（）一起为双碳-碳键（C=C）时；R10为从R10.1-R10.5中选择的取代基；R10.1 R10.2 R10.4 R10.5；R11为从H、F、Cl、CH3或CF3中选择的取代基；R12为氢、C1-C4-烷基或C3-C6-环烷基；X为氧或乙烯二基-1,1（C=CH2）；Y为O、S、CH2或HO-CH基，提供当连续线及其相应的虚线（式7）一起为单碳-碳（C-C）键时，或Y为CH基，提供当连续线及其相应的虚线（式7）一起为双碳-碳键（C=C）时，以及通用式（1）的化合物、立体异构体、同位素富集类似物、药学上可接受的盐、水合物、溶剂合物或晶体或多形式，其中：Ar为芳基或杂芳基；R1为H或CH3；R2为异丙基；Nuc为式（8）、（9）或（10）。
• 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。
• Combination formulation of three antiviral compounds
  申请人：Gilead Pharmasset LLC

  公开号：US10912814B2

  公开（公告）日：2021-02-09

  Disclosed are pharmaceutical compositions comprising three antiviral compounds. In particular, the pharmaceutical compositions comprise an effective amount of velpatasvir, an effective amount of sofosbuvir, and an effective amount of voxilaprevir. Also disclosed are methods of use for the pharmaceutical composition.

  本发明公开了包含三种抗病毒化合物的药物组合物。特别是，药物组合物包含有效量的 velpatasvir、有效量的 sofosbuvir 和有效量的 voxilaprevir。还公开了药物组合物的使用方法。
• COMBINATION FORMULATION OF THREE ANTIVIRAL COMPOUNDS
  申请人：Gilead Pharmasset LLC

  公开号：US20170360874A1

  公开（公告）日：2017-12-21

  Disclosed are pharmaceutical compositions comprising three antiviral compounds. In particular, the pharmaceutical compositions comprise an effective amount of velpatasvir, an effective amount of sofosbuvir, and an effective amount of voxilaprevir. Also disclosed are methods of use for the pharmaceutical composition.
• US8551973B2
  申请人：——

  公开号：US8551973B2

  公开（公告）日：2013-10-08