diisopropyl (diisopropoxyphosphorylmethylsulfonylmethyl)phosphonate | 1015692-34-8

• 物质功能分类: 化学试剂 - 有机试剂 - 膦酸酯/膦酸盐
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diisopropyl (diisopropoxyphosphorylmethylsulfonylmethyl)phosphonate
• 英文别名: Tetraisopropyl (sulfonylbis(methylene))bis(phosphonate)；2-[di(propan-2-yloxy)phosphorylmethylsulfonylmethyl-propan-2-yloxyphosphoryl]oxypropane
• CAS: 1015692-34-8
• 化学式: C₁₄H₃₂O₈P₂S
• 分子量: 422.417
• InChiKey: FQTPDRYZRLTVCZ-UHFFFAOYSA-N

物化性质

• 熔点：
  102.5-104.5 °C(Solvent: Diethyl ether ; Hexane)
• 沸点：
  526.5±35.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diisopropyl (diisopropoxyphosphorylmethylsulfonylmethyl)phosphonate 在 4,5-二氰基咪唑 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 N,N-二异丙基乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 15.0~20.0 ℃ 、103.42 kPa 条件下， 反应 7.25h， 生成 3-[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-2-[2-[di(propan-2-yloxy)phosphorylmethylsulfonyl]ethyl]-4-methoxyoxolan-3-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
  参考文献：
  名称：

  [EN] SHORT INTERFERING NUCLEIC ACID (SINA) MOLECULES AND USES THEREOF FOR CORONAVIRUS DISEASES
  [FR] MOLÉCULES D'ACIDE NUCLÉIQUE INTERFÉRENT COURT (SINA) ET LEURS UTILISATIONS POUR LES MALADIES À CORONAVIRUS

  摘要：

  本发明涉及制药化合物和制剂领域，以及它们在治疗疾病中的使用方法。描述了包含修饰核苷酸的短干扰核酸（siNA）分子，含有这些分子的组合物，以及用于治疗或预防冠状病毒感染的用途。具体来说，本发明涉及对广泛谱的冠状病毒，尤其是β-冠状病毒，包括引发COVID-19的SARS-CoV-2的有效siNA分子领域。

  公开号：

  WO2021207637A1
• 作为产物：
  描述：

  diisopropyl (mercaptomethyl) phosphonate 在 oxone 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 24.0h， 生成 diisopropyl (diisopropoxyphosphorylmethylsulfonylmethyl)phosphonate
  参考文献：
  名称：

  [EN] SHORT INTERFERING NUCLEIC ACID (SINA) MOLECULES AND USES THEREOF FOR CORONAVIRUS DISEASES
  [FR] MOLÉCULES D'ACIDE NUCLÉIQUE INTERFÉRENT COURT (SINA) ET LEURS UTILISATIONS POUR LES MALADIES À CORONAVIRUS

  摘要：

  本发明涉及制药化合物和制剂领域，以及它们在治疗疾病中的使用方法。描述了包含修饰核苷酸的短干扰核酸（siNA）分子，含有这些分子的组合物，以及用于治疗或预防冠状病毒感染的用途。具体来说，本发明涉及对广泛谱的冠状病毒，尤其是β-冠状病毒，包括引发COVID-19的SARS-CoV-2的有效siNA分子领域。

  公开号：

  WO2021207637A1

文献信息

• Synthesis of sulfone-based nucleotide isosteres: identification of CMP-sialic acid synthetase inhibitors
  作者：Jessica H. Wong、Urvashi Sahni、Yanhong Li、Xi Chen、Jacquelyn Gervay-Hague

  DOI：10.1039/b819155g

  日期：——

  A modular replacement approach to the synthesis of sulfo-nucleotide analogs prepared from condensation of nucleoside aldehydes with bis phosphonate Horner-Wadsworth-Emmons reagents is disclosed. These analogs were shown to be inhibitors of Neisseria meningitidis CSS (NmCSS), which is a key enzyme in the biosynthesis of the capsular polysaccharides required for bacterial infection.

  一种模块化替代方法用于合成由核苷醛与双磷酸酯Horner-Wadsworth-Emmons试剂缩合制备的磺酸核苷类似物。研究表明，这些类似物是脑膜炎奈瑟氏菌CSS（NmCSS）的抑制剂，该酶在细菌感染所需的荚膜多糖的生物合成中起关键作用。
• Synthesis of (sulfonyl)methylphosphonate analogs of prenyl diphosphates
  作者：Michael W. Lodewyk、Victor G. Lui、Dean J. Tantillo

  DOI：10.1016/j.tetlet.2009.10.119

  日期：2010.1

  Syntheses of several (sulfonyl)methylphosphonate analogs of geranyl, neryl, and farnesyl diphosphates are described. Key steps include utilization of an (E)-selective Horner–Wadsworth–Emmons olefination which couples an aldehyde to the sulfone phosphonate moiety, and a selective reduction of the resulting dienyl sulfone phosphonate substrates.

  描述了香叶基，磷酸基和法呢基二磷酸的几种（磺酰基）甲基膦酸酯类似物的合成。关键步骤包括利用将醛与砜膦酸酯部分偶联的（E）选择性Horner-Wadsworth-Emmons烯烃化反应，以及选择性还原所得的二烯基砜膦酸酯底物。
• Vinyl sulfones
  作者：Jessica H. Wong、Marilyn M. Olmstead、James C. Fettinger、Jacquelyn Gervay-Hague

  DOI：10.1107/s0108270108002692

  日期：2008.3.15

  Four neutral vinyl sulfones, two of which are paired with phosphonate groups, are described. The compounds are diisopropyl (2-phenylethenylsulfonylmethyl) phosphonate, C15H23O5PS, (I), diisopropyl [2-(7-methoxy-1,3-benzodioxol-5-yl) ethenylsulfonyl]methylsulfonylmethyl} phosphonate, C18H27O10PS2, (II), bis(trans-2-phenylethenyl) sulfone, C16H14O2S, (III), and bis(trans-2-phenylethenylsulfonyl) methane, C17H16O4S2, (IV). Their structures can be considered as highly functionalized mimics of mono-, di- and triphosphates. These phosphate isosteres are currently of interest as agents for enzyme inhibition in both cancer and HIV therapy. All except one of the compounds has Z' > 1. The lone exception is (IV), a disulfone with twofold crystallographic symmetry. Geometrically, the sulfone functionality is found to be a good mimic for phosphate. The principal effect of the vinyl group is to shorten the S-C(vinyl) distance relative to the S-CH2 distance by ca 0.05 angstrom. The S-C-S and S-C-P backbones resemble the P-O-P backbone but are not identical because the S - C and P - C distances are longer than the P-O distance and the S-C-S and S-C-P angles are more acute than the P-O-P angle. No prior crystal structures of comparable compounds have been published.
• [EN] PNPLA3-TARGETING SHORT INTERFERING RNA (SIRNA) MOLECULES AND USES THEREOF<br/>[FR] MOLÉCULES D'ARN INTERFÉRENT COURT (ARNSI) CIBLANT PNPLA3 ET LEURS UTILISATIONS
  申请人：[en]ALIGOS THERAPEUTICS, INC.

  公开号：WO2023034937A1

  公开（公告）日：2023-03-09

  Disclosed herein are short interfering RNA (siRNA) molecules that downregulate expression of PNPLA3 or variants thereof. The siRNA molecules comprise modified nucleotides and uses thereof. The siRNA molecules may be double stranded and comprise modified nucleotides, such as 2'-O-methyl nucleotides and 2'-fluoro nucleotides, and ligands.
• [EN] SHORT INTERFERING NUCLEIC ACID (SINA) MOLECULES AND USES THEREOF FOR CORONAVIRUS DISEASES<br/>[FR] MOLÉCULES D'ACIDE NUCLÉIQUE INTERFÉRENT COURT (SINA) ET LEURS UTILISATIONS POUR LES MALADIES À CORONAVIRUS
  申请人：ALIGOS THERAPEUTICS INC

  公开号：WO2021207637A1

  公开（公告）日：2021-10-14

  The present invention is in the field of pharmaceutical compounds and preparations and method of their use in the treatment of disease. Described are short interfering nucleic acid (siNA) molecules comprising modified nucleotides, compositions containing the same, and uses thereof for treating or preventing coronavirus infections. In particular, the present invention is in the field of siNA molecules effective against a broad spectrum of coronaviruses, and especially the β-coronaviruses, including SARS-CoV-2, the causative agent of COVID-19.

  本发明涉及制药化合物和制剂领域，以及它们在治疗疾病中的使用方法。描述了包含修饰核苷酸的短干扰核酸（siNA）分子，含有这些分子的组合物，以及用于治疗或预防冠状病毒感染的用途。具体来说，本发明涉及对广泛谱的冠状病毒，尤其是β-冠状病毒，包括引发COVID-19的SARS-CoV-2的有效siNA分子领域。