[[(bis[[(2,2-dimethylpropanoyl)oxy]methoxy]phosphoryl)methyl([(2,2-dimethylpropanoyl)oxy]methoxy)phosphoryl]oxy]methyl 2,2-dimethylpropanoate | 134606-34-1

• 物质功能分类: 化学试剂 - 有机试剂 - 含磷化合物
• 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: [[(bis[[(2,2-dimethylpropanoyl)oxy]methoxy]phosphoryl)methyl([(2,2-dimethylpropanoyl)oxy]methoxy)phosphoryl]oxy]methyl 2,2-dimethylpropanoate
• 英文别名: tetra(pivaloyloxymethyl) methylenebisphosphonate；tetra(pivaloyloxymethyl)-bisphosphonate；Tetrakis[(pivaloyloxy)methyl] methylenediphosphonate；[bis(2,2-dimethylpropanoyloxymethoxy)phosphorylmethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
• CAS: 134606-34-1
• 化学式: C₂₅H₄₆O₁₄P₂
• 分子量: 632.579
• InChiKey: UNXRGZHZKHCCJB-UHFFFAOYSA-N

物化性质

• 熔点：
  68-72°C
• 沸点：
  636.0±55.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  41
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  176
• 氢给体数：
  0
• 氢受体数：
  14

安全信息

• 储存条件：
  -20°C, in an inert atmosphere

反应信息

• 作为反应物：
  描述：

  [[(bis[[(2,2-dimethylpropanoyl)oxy]methoxy]phosphoryl)methyl([(2,2-dimethylpropanoyl)oxy]methoxy)phosphoryl]oxy]methyl 2,2-dimethylpropanoate 在 sodium hypochlorite 、 碳酸氢钠 作用下， 反应 0.5h， 以66%的产率得到tetra(pivaloyloxymethyl) (dichloromethylene)bisphosphonate
  参考文献：
  名称：

  双膦酸酯前药：亚甲基双膦酸酯的四酰氧基甲基酯的新合成策略

  摘要：

  提出了一种简洁，简便的方法，从H 2 C [P（O）（OMe）2 ] 2开始以高选择性和合理的收率制备Cl 2 C [P（O）（OCH 2 O 2 CCMe 3）2 ] 2。。

  DOI：

  10.1016/s0040-4039(99)01799-2
• 作为产物：
  描述：

  特戊酸氯甲酯 在 silver nitrate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 [[(bis[[(2,2-dimethylpropanoyl)oxy]methoxy]phosphoryl)methyl([(2,2-dimethylpropanoyl)oxy]methoxy)phosphoryl]oxy]methyl 2,2-dimethylpropanoate
  参考文献：
  名称：

  双膦酸酯前药：亚甲基双膦酸酯的四酰氧基甲基酯的新合成策略

  摘要：

  提出了一种简洁，简便的方法，从H 2 C [P（O）（OMe）2 ] 2开始以高选择性和合理的收率制备Cl 2 C [P（O）（OCH 2 O 2 CCMe 3）2 ] 2。。

  DOI：

  10.1016/s0040-4039(99)01799-2

文献信息

• [EN] S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS<br/>[FR] POLYMÈRES OLIGONUCLÉOTIDIQUES INHIBANT LE TRANSPORT DE L'ANTIGÈNE S ET MÉTHODES
  申请人：ALIGOS THERAPEUTICS INC

  公开号：WO2021119325A1

  公开（公告）日：2021-06-17

  Various embodiments provide STOPS™ polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS™ modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS™ modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.

  各种实施方式提供了STOPS™聚合物，这些聚合物是S-抗原转运抑制寡核苷酸聚合物，提供了制备它们的方法以及使用它们治疗疾病和症状的方法。在某些实施方式中，STOPS™修饰的寡核苷酸包括至少部分磷硫酸酯化的交替A和C单元序列，具有如本文所述的修饰。通过HBsAg分泌测定确定的STOPS™修饰的寡核苷酸对乙型肝炎的序列无关抗病毒活性，其EC50小于100 nM。
• Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors
  申请人：Merck & Co., Inc.

  公开号：US05227506A1

  公开（公告）日：1993-07-13

  The invention relates to acyloxymethyl esters of bisphosphonic acids, halo-bisphosphonic acids and hydroxy-bisphosphonic acids which exhibit oral bioavailability and are useful in the treatment of disturbances involving calcium or phosphate metabolism, in particular, the treatment and prevention of diseases involving bone resorption, especially osteoporosis, Paget's disease, malignant hypercalcemia, and metastatic bone disease.

  该发明涉及酰氧甲基双膦酸酯、卤代双膦酸和羟基双膦酸，具有口服生物利用度，并且在治疗涉及钙或磷代谢紊乱的疾病中有用，特别是在治疗和预防涉及骨吸收的疾病方面，尤其是骨质疏松症、帕盖特病、恶性高钙血症和转移性骨病方面。
• [EN] NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSITIONS D'ACIDE NUCLÉIQUE-POLYPEPTIDE ET UTILISATIONS DE CELLES-CI
  申请人：AVIDITY BIOSCIENCES LLC

  公开号：WO2019071028A1

  公开（公告）日：2019-04-11

  Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

  本文披露了包含与修饰的多核苷酸分子和聚合物结合基团的组合物和药物配方。本文还描述了利用包含与多核苷酸分子和聚合物结合基团共轭的组合物或药物配方治疗癌症的方法。
• Synthesis of 5′-Methylene-Phosphonate Furanonucleoside Prodrugs: Application to <scp>D</scp>-2′-Deoxy-2′-α-fluoro-2′-β-<i>C</i>-methyl Nucleosides
  作者：Ugo Pradere、Franck Amblard、Steven J. Coats、Raymond F. Schinazi

  DOI：10.1021/ol301937v

  日期：2012.9.7

  A new and facile synthetic pathway to metabolically stable 5′-methylene-bis(pivaloyloxymethyl)(POM)phosphonate furanonucleoside prodrugs is reported. The key step involves a Horner–Wadsworth–Emmons reaction of a tetra(pivaloyloxymethyl) bisphosphonate salt with appropriately protected 5′-aldehydic nucleosides. This efficient approach was applied for the synthesis HCV related 2′-deoxy-2′-α-fluoro-2′-β-C-methyl

  报道了代谢稳定的 5'-亚甲基-双（新戊酰氧基甲基）（POM）膦酸酯呋喃核苷前药的新且简便的合成途径。关键步骤涉及四（新戊酰氧基甲基）二膦酸盐与适当保护的 5'-醛核苷的霍纳-沃兹沃斯-埃蒙斯反应。这种有效的方法被应用于合成HCV相关的2'-脱氧-2'-α-氟-2'-β- C-甲基核苷。
• [EN] MODIFIED DOUBLE-STRANDED RNA AGENTS<br/>[FR] AGENTS D'ARN DOUBLE BRIN MODIFIÉ
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2016028649A1

  公开（公告）日：2016-02-25

  One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2'-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

  本发明的一个方面涉及能够抑制靶基因表达的双链RNA（dsRNA）试剂。dsRNA试剂的sense链包含至少一个热不稳定核苷酸，并且至少一个该热不稳定核苷酸出现在与antisense链的seed区域（位置2-8）相对的位置上；dsRNA试剂的antisense链包含至少两个修饰核苷酸，这些核苷酸提供的立体体积小于或等于2'-OMe修饰的立体体积，其中这些修饰的核苷酸相隔11个核苷酸长度。该发明的其他方面涉及包含这些dsRNA试剂的药物组合物，适用于治疗用途，并通过给予这些dsRNA试剂的方法来抑制靶基因的表达，例如用于治疗各种疾病条件。