S-pivaloyl-2-thioethyl di(N,N-diisopropylamino)phosphoramidite | 200502-01-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 硫代羧酸及其衍生物
• 英文名称: S-pivaloyl-2-thioethyl di(N,N-diisopropylamino)phosphoramidite
• 英文别名: (S-pivaloyl-2-thioethyl)-N,N-bis(diisopropylamino)phosphine；S-2-(bis(diisopropylamino)phosphinooxy)ethyl 2,2-dimethylpropanethioate；S-[2-bis[di(propan-2-yl)amino]phosphanyloxyethyl] 2,2-dimethylpropanethioate
• CAS: 200502-01-8
• 化学式: C₁₉H₄₁N₂O₂PS
• 分子量: 392.587
• InChiKey: MNVVYDAOFGGZPN-UHFFFAOYSA-N

物化性质

• 沸点：
  427.5±47.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  58.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  S-pivaloyl-2-thioethyl di(N,N-diisopropylamino)phosphoramidite 在 四氮唑 、 盐酸 、 叔丁基过氧化氢 、 二异丙胺 作用下， 以 乙醚 、 甲苯 、 乙腈 为溶剂， 生成 O-(L-tert-butoxytyrosinyl) O-(S-pivaloyl-2-thioethyl) 3'-azido-2',3'-deoxythymidin-5'-yl phosphate hydrochloride
  参考文献：
  名称：

  DESIGN OF NEW MONONUCLEOTIDE PRODRUGS: ARYL (SATE) PHOSPHOTRIESTER DERIVATIVES

  摘要：

  Synthesis, biological activities and decomposition kinetics of novel phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-tButyl-2-thioethyl (tBuSATE) group and L-tyrosinyl residues are reported. All the derivatives appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments. The proposed decomposition process of these mixed phosphotriesters may involve successively an esterase and then a phosphodiesterase activation.

  DOI：

  10.1081/ncn-100002302
• 作为产物：
  描述：

  双二异丙基氨基氯化磷 、 S-(2-羟乙基)2,2-二甲基丙硫酸盐 在 三乙胺 作用下， 以 乙醚 为溶剂， 反应 2.0h， 以88%的产率得到S-pivaloyl-2-thioethyl di(N,N-diisopropylamino)phosphoramidite
  参考文献：
  名称：

  AZT的5'-氟代磷酸酯衍生物的合成，抗HIV活性和稳定性研究。

  摘要：

  报道了3'-叠氮基-3'-脱氧胸苷（AZT）的5'-氟磷酸盐衍生物的合成，体外抗HIV活性和稳定性研究。结果支持这样的假设，即该磷酸化的实体通过酶促过程通过递送相应的5'-单核苷酸来发挥其生物学作用。但是，在缺乏胸苷激酶的CEM细胞中进行的抗病毒评估以及在培养基和细胞提取物中的稳定性研究表明，这种生物转化并非特定于细胞内培养基。据报道，尝试通过使用S-新戊酰基-2-硫代乙基（tBuSATE）基团作为生物不稳定的磷酸盐保护来改善单核苷5'-氟磷酸盐的生物活性。

  DOI：

  10.1006/bioo.2001.1220

文献信息

• Synthesis and Evaluation of Double-Prodrugs against HIV. Conjugation of D4T with 6-Benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, Emivirine)-Type Reverse Transcriptase Inhibitors via the SATE Prodrug Approach
  作者：Lene Petersen、Per T. Jørgensen、Claus Nielsen、Thomas H. Hansen、John Nielsen、Erik B. Pedersen

  DOI：10.1021/jm040845b

  日期：2005.2.1

  between d4T monophosphate and the known NNRTI MKC-442, which were linked through a labile p-hydroxybenzoyl protection group in the N-3 position of MKC-442. Double-prodrugs 2 and 3 were conjugates between d4T monophosphate and the new NNRTIs 15 and 19 linked through a stable phenolic linker that was a part of the N-1 substituents of the NNRTIs. The double-prodrugs 1, 2, and 3 all had good activities against

  本文报道了基于已知的混合SATE（S-酰基-2-硫代乙基）前药方法的新型双重前药对HIV的合成和抗病毒活性。核苷逆转录酶抑制剂（NRTI）d4T的单磷酸酯被一个SATE基团和一个芳香基团掩盖，通过该基团连接了一个非核苷逆转录酶抑制剂（NNRTI）。双前药1是d4T单磷酸酯与已知的NNRTI MKC-442的混合物，后者通过MKC-442的N-3位上不稳定的对羟基苯甲酰基保护基连接。双前药2和3是d4T单磷酸酯与新的NNRTI 15和19之间的结合物，新NNRTI 15和19通过稳定的酚类连接基连接，该连接基是NNRTIs N-1取代基的一部分。双前药1、2和3对野生型HIV-1，Y181C突变体均具有良好的活性，
• 2'-CHLORO NUCLEOSIDE ANALOGS FOR HCV INFECTION
  申请人：Idenix Pharmaceuticals, Inc.

  公开号：US20140099283A1

  公开（公告）日：2014-04-10

  Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2′-chloro nucleosides according to Formula 2001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.

  本文提供了用于治疗黄病毒科感染，包括丙型肝炎感染的化合物、组合物和方法。在某些实施例中，揭示了核苷衍生物化合物和组合物，可以单独或与其他抗病毒药物联合给药。在某些实施例中，化合物是根据2001年公式的2'-氯核苷，或其药用可接受的盐、溶剂合物、立体异构体形式、互变异构体形式或多晶形式，其中B、Z和PD如本文所述。
• TRANSDUCIBLE DELIVERY OF NUCLEIC ACIDS BY REVERSIBLE PHOSPHOTRIESTER CHARGE NEUTRALIZATION PROTECTING GROUPS
  申请人：Dowdy Steven F.

  公开号：US20090093425A1

  公开（公告）日：2009-04-09

  This disclosure relates to nucleic acid constructs modified to have a reduced net anionic charge. In some aspects the constructs comprise phosphodiester and/or phosphothioate protecting groups. The disclosure also provide methods of making and using such constructs.

  本披露涉及修饰为减少净阴离子电荷的核酸构建物。在某些方面，构建物包括磷酸二酯和/或磷酸硫酯保护基团。本披露还提供了制备和使用此类构建物的方法。
• WO2008/8476
  申请人：——

  公开号：——

  公开（公告）日：——
• Photocleavable Protecting Groups as Nucleobase Protections Allowed the Solid-Phase Synthesis of Base-Sensitive SATE-Prooligonucleotides
  作者：Karine Alvarez、Jean-Jacques Vasseur、Thierry Beltran、Jean-Louis Imbach

  DOI：10.1021/jo990479h

  日期：1999.8.1

  The first synthesis of oligodeoxynucleotide heteropolymers carrying base-sensitive S-pivaloylthioethyl (t-Bu-SATE) phosphotriester linkages has been performed. It is based on the use of 6-nitroveratryloxycarbonyl (NVOC) and 2,2'-bis(2-nitrophenyl)ethoxycarbonyl (diNPEOC) groups as nucleobase protections in combination with photolysis deprotection. The synthesis was realized using the phosphoramidite approach on solid support bearing a 1-(o-nitrophenyl)-1,3-propanediol linker. The removal of the protecting groups and the cleavage of the oligonucleotides from the solid support were accomplished in a single photolysis procedure upon UV irradiation at wavelengths >300 nn. Faster deprotection rates were observed for diNPEOC-protected nucleosides and oligomers than with NVOC-protected ones. The synthesis of pentanucleoside t-Bu-SATE-phosphotriesters d((5')TpCpCpCpTp(3')), d((5')TpApApApAp(3')), and d((5')TpGpGpGpTp(3')) and of dodecanucleoside t-Bu-SATE-phosphotriesters and -phosphorothioate d((5')ApCpApCpCpCpApApTpTpCpTp(3')) and d((5')ApGpApApTpTpGpGpGpTpGpTp(3')) demonstrated the efficiency of the method.