ethyl (N,N,N',N'-tetraisopropyl)phosphorodiamidite | 30463-60-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl (N,N,N',N'-tetraisopropyl)phosphorodiamidite
• 英文别名: ethyl N,N,N’,N’-tetraisopropylphosphorodiamidite；N-[[di(propan-2-yl)amino]-ethoxyphosphanyl]-N-propan-2-ylpropan-2-amine
• CAS: 30463-60-6
• 化学式: C₁₄H₃₃N₂OP
• 分子量: 276.403
• InChiKey: ZYQPNKHEEHSDCO-UHFFFAOYSA-N

物化性质

• 沸点：
  304.5±25.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  15.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (N,N,N',N'-tetraisopropyl)phosphorodiamidite 在 二异丙基铵盐四氮唑 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 14.0h， 生成 [[di(propan-2-yl)amino]-ethoxy-[(3R,4S,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxyphosphaniumyl]-phenylazanide
  参考文献：
  名称：

  Glycosyl Phosphoramidimidates as Versatile Glycosyl Donors

  摘要：

  DOI：

  10.3987/com-96-7466
• 作为产物：
  描述：

  乙基二氯磷酸酯 、 二异丙胺 以 乙醚 为溶剂， 反应 1.0h， 以45%的产率得到ethyl (N,N,N',N'-tetraisopropyl)phosphorodiamidite
  参考文献：
  名称：

  General Synthesis and Binding Affinity of Position-Selective Phosphonodiester- and Phosphotriester-Incorporated Oligodeoxyribonucleotides

  摘要：

  Synthesis of phosphonodiester- and phosphotriester-modified oligodeoxyribonucleotides has been accomplished via the phosphoramidite approach with allylic protection. The modification can be made at the selected position(s) of the oligomers. The efficiency of this method has been demonstrated by the synthesis of base-labile modified oligo(deoxyribonucleotide)s such as the methyl phosphates and phenylphosphonates. Melting temperatures of the duplexes containing these artificial strands indicate that the backbone-alternation, which is made at a single site, does not have a negative influence on the binding affinity to the complementary DNA.

  DOI：

  10.1021/jo00109a024

文献信息

• 2'-CYANO SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF USEFUL FOR THE TREATMENT OF VIRAL DISEASES
  申请人：Girijavallabhan Vinay

  公开号：US20140161770A1

  公开（公告）日：2014-06-12

  The present invention relates to 2′-Cyano Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R 1 , R 2 and R 3 are as defined herein. The present invention also relates to compositions comprising at least one 2′-Cyano Substituted Nucleoside Derivative, and methods of using the 2′-Cyano Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

  本发明涉及式(I)的2'-氰基取代核苷衍生物及其药学上可接受的盐，其中B、X、R1、R2和R3如本文所定义。本发明还涉及包含至少一种2'-氰基取代核苷衍生物的组合物，以及使用这些2'-氰基取代核苷衍生物治疗或预防患者HCV感染的方法。
• [EN] MODIFIED CYCLIC DINUCLEOSIDE COMPOUNDS AS STING MODULATORS<br/>[FR] COMPOSÉS DI-NUCLÉOSIDIQUES CYCLIQUES MODIFIÉS SERVANT DE MODULATEURS STING
  申请人：ALIGOS THERAPEUTICS INC

  公开号：WO2020227421A1

  公开（公告）日：2020-11-12

  Provided herein are compounds of Formula (I), Formula (II) and/or Formula (III), or pharmaceutically acceptable salts of any of the foregoing, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), Formula (II) and/or Formula (III), or a pharmaceutically acceptable salt of any of the foregoing.

  本文提供了Formula (I)、Formula (II)和/或Formula (III)的化合物，或者上述任何一个的药用盐，包括本文描述的化合物（包括本文描述的化合物的药用盐）的药物组合物和合成方法。本文还提供了使用Formula (I)、Formula (II)和/或Formula (III)的化合物，或者上述任何一个的药用盐来治疗疾病和/或症状的方法。
• 2′-Deoxy-2′-α-fluoro-2′-β-C-methyl 3′,5′-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: Discovery of PSI-352938
  作者：P. Ganapati Reddy、Donghui Bao、Wonsuk Chang、Byoung-Kwon Chun、Jinfa Du、Dhanapalan Nagarathnam、Suguna Rachakonda、Bruce S. Ross、Hai-Ren Zhang、Shalini Bansal、Christine L. Espiritu、Meg Keilman、Angela M. Lam、Congrong Niu、Holly Micolochick Steuer、Phillip A. Furman、Michael J. Otto、Michael J. Sofia

  DOI：10.1016/j.bmcl.2010.10.035

  日期：2010.12

  A series of novel 2′-deoxy-2′-α-fluoro-2′-β-C-methyl 3′,5′-cyclic phosphate nucleotide prodrug analogs were synthesized and evaluated for their in vitro anti-HCV activity and safety. These prodrugs demonstrated a 10–100-fold greater potency than the parent nucleoside in a cell-based replicon assay due to higher cellular triphosphate levels. Our structure–activity relationship (SAR) studies provided

  合成了一系列新型 2'-deoxy-2'-α-fluoro-2'-β- C-甲基 3',5'-环状磷酸核苷酸前药类似物，并对其体外抗 HCV 活性和安全性进行了评估。由于更高的细胞三磷酸盐水平，这些前药在基于细胞的复制子测定中显示出比母体核苷高 10-100 倍的效力。我们的构效关系 (SAR) 研究提供了在大鼠口服给药时在大鼠肝脏中产生高水平活性三磷酸盐的化合物。这些研究最终导致了临床开发候选者24a (PSI-352938) 的选择。
• Modified oligonucleotides and compound that can be used for synthesizing same
  申请人：GUANGZHOU RIBOBIO CO., LTD.

  公开号：US20200369703A1

  公开（公告）日：2020-11-26

  The present disclosure falls within the field of biomedical technology, and in particular relates to modified oligonucleatides and a compound that can be used for synthesizing same and a method for modifying oligonucleotides. The present disclosure also relates to the use of the modified oligonucleotides for preventing and/or treating diseases associated with the liver in a subject.

  本公开涉及生物医学技术领域，特别是涉及改良寡核苷酸和一种可用于合成相同的化合物以及一种修改寡核苷酸的方法。本公开还涉及使用改良寡核苷酸来预防和/或治疗与主体肝脏相关的疾病。
• Cytotoxic and mutagenic properties of alkyl phosphotriester lesions in Escherichia coli cells
  作者：Jiabin Wu、Pengcheng Wang、Yinsheng Wang

  DOI：10.1093/nar/gky140

  日期：2018.5.4

  translesion synthesis DNA polymerases. In this study, we synthesized oligodeoxyribonucleotides containing four pairs (Sp and Rp) of alkyl phosphotriester lesions at a defined site, and examined how these lesions are recognized by DNA replication machinery in Escherichia coli cells. We found that the Sp diastereomer of the alkyl phosphotriester lesions could be efficiently bypassed, whereas the Rp counterparts

  暴露于许多内源性和外源性物质会引起DNA烷基化，这是DNA损伤的主要类型。在DNA烷基化产物中，烷基磷酸三酯的出现频率较高，并且对哺乳动物组织的修复具有抵抗力。但是，关于这些损伤如何影响细胞中DNA复制的效率和保真度或如何通过跨病变合成DNA聚合酶调节这些损伤的复制旁路知之甚少。在这项研究中，我们合成了在定义的位点包含四对（S p和R p）烷基磷酸三酯病变的寡脱氧核糖核苷酸，并研究了这些病变如何被大肠杆菌中的DNA复制机制识别细胞。我们发现，烷基磷酸三酯病变的S p非对映异构体可以被有效地绕过，而R p对应物适度地阻断了DNA复制。而且，S p-甲基磷酸三酯在侧翼的TT二核苷酸位点诱导TT→GT和TT→GC突变，并且这些突变的诱导需要Ada蛋白，已知该蛋白可有效地从S p-甲基磷酸三酯中除去甲基。 。总之，我们的研究提供了对细胞中DNA复制机制对烷基磷酸三酯损伤识别的全面理解，并首次揭示了