3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile | 138800-31-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 138800-31-4
• 化学式: C₁₉H₃₀N₇O₅P
• 分子量: 467.465
• InChiKey: GOZJMOKZBGZWKJ-ZKHLZZRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile 在 四氮唑 、 甲醇 、 氨 、 碘 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 2(S)-(hydroxy(3-deoxy-3-azidothymidyl)phosphorylamino)-3-(3-indolyl)propionic acid methyl ester
  参考文献：
  名称：

  A Phosphoramidite-Based Synthesis of Phosphoramidate Amino Acid Diesters of Antiviral Nucleosides

  摘要：

  A general synthetic procedure is presented for the preparation of 5'-amino acid phosphoramidates of zidovudine (AZT), 3'-deoxy-2',3'-didehydrothymidine (D4T), and 3'-fluoro-3'-deoxythymidine (FLT) from their corresponding phosphoramidites. These water soluble amino acid phosphoramidates are more non-polar than the parent nucleoside and exhibit high stability in aqueous media.

  DOI：

  10.1080/15257779408010671
• 作为产物：
  描述：

  2-氰乙基N,N-二异丙基氯亚磷酰胺 、 齐多夫定 在 DIPAE 作用下， 以 乙腈 为溶剂， 生成 3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
  参考文献：
  名称：

  Synthesis of AZT-α-Borano-5′-Diphospho-Hexoses

  摘要：

  3'-Azido-3'-deoxythymidine-alpha-boranq-5'-disphospho-hexoses have been have been synthesized. Their diastereoisomers were separated by HPLC.

  DOI：

  10.1080/15257779908041637

文献信息

• Synthesis and Anti-HIV Activity of Alkyl Steroidal 3′-Azido-3′-deoxythymidin-5′-yl Phosphotriesters as Prodrugs of AZT
  作者：Meher I. Balagopala、Abraham P. Ollapally、Henry J. Lee

  DOI：10.1080/15257779408010667

  日期：1994.9

  Alkyl steroidal AZT 5'-monophosphate triesters are designed as lipophilic prodrugs of AZT to improve its therapeutic efficiency. We have synthesized four phosphotriesters of AZT, in one-pot, using phosphoramidite-phosphite triester methodology. This method afforded the desired prodrugs in high yields under mild conditions. The in vitro evaluation of anti-HIV activity of these prodrugs is also reported.
• O-Alkyl-5',5'-dinucleoside phosphates as prodrugs of 3'-azidothymidine and cordycepin
  作者：Chris Meier、Jean Michel Neumann、Francois Andre、Yvette Henin、Huynh Dinh Tam

  DOI：10.1021/jo00052a053

  日期：1992.12

  The syntheses of two O-alkyl-5',5'-dinucleoside phosphotriesters 2a and 2b as combined prodrugs of the antiviral drug AZT (1) and the antibiotic agent cordycepin (3) are described. 2a,b were obtained as a 1:1 diastereomeric mixture. The absolute configuration of the isolated diastereomers was determined by NOE NMR experiments and correlated with the migration characteristics on silica gel as well as the P-31-NMR chemical shift. The conformational features of 2b(R) and 2b(S) were determined m deuteriated dodecylphosphocholine micelles in aqueous solution using 2D-NOESY spectra and shown to be dependent on the configuration at phosphorus. Additionally, all new compounds were tested for their antiviral activities in HIV-1-infected CEM C113 and H9 cell systems. Although all compounds were able to significantly inhibit the HIV-1-induced cytopathogenic effect, only the phosphodiester 12 gave a selectivity index (SI(RT) = 2000) comparable to the reference compound AZT (1) (SI(RT) = 3000).