N-myristoyl-Glu(OtBu)-OH | 1365246-87-2

• 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: N-myristoyl-Glu(OtBu)-OH
• 英文别名: (2S)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(tetradecanoylamino)pentanoic acid
• CAS: 1365246-87-2
• 化学式: C₂₃H₄₃NO₅
• 分子量: 413.598
• InChiKey: PFGRTVHCSCWHAZ-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  29
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-myristoyl-Glu(OtBu)-OH 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以82%的产率得到N-(1-氧代十四烷基)-L-谷氨酸(9CI)
  参考文献：
  名称：

  N-Myristoylglutamic acid derivative of 3′-fluoro-3′-deoxythymidine as an organogel

  摘要：

  Designing microbicidal gels of anti-HIV drugs for local application to prevent HIV infection is a subject of major interest. 3'-Fluoro-3'-deoxythymidine (FLT), a nucleoside reverse transcriptase inhibitor (NRTI), was conjugated with a N-myristoylglutamate scaffold. The conjugate showed gelation at 1% (w/w) in different organic solvents, such as toluene, dichloromethane, and chloroform. The gels were opaque and stable at room temperature. The results indicate that myristoyl glutamate derivative of FLT can form an organogel. The gel could have potential application as a topical anti-HIV microbicidal agent. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.07.101
• 作为产物：
  描述：

  L-谷氨酸-5-叔丁基酯 、 肉豆蔻酸酐 在 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 4.0h， 以91%的产率得到N-myristoyl-Glu(OtBu)-OH
  参考文献：
  名称：

  Synthesis and Anti-HIV Activities of Glutamate and Peptide Conjugates of Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Mono-, di-, and trinucleoside conjugates of glutamate or peptide scaffolds containing nucleoside reverse transcriptase inhibitors were synthesized. Among dinucleoside glutamate ester derivatives, N-myristoylated derivatives showed significantly higher anti-HIV activity than the corresponding N-acetylated conjugates against cell-free virus. Myristoyl-Glu(3TC)-FLT (46, EC50 = 0.3-0.6 mu M) and myristoyl-Glu(FTC)-FLT (47, EC50 = 0.1-0.4 mu M) derivatives were the most active glutamate-dinucleoside conjugates. A trinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC50 = 0.9-1.4 mu M) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus. Compound 34 also exhibited higher anti-HIV activity against multidrug (IC50 = 5.9 nM) and NNRTI (IC50 = 12.9 nM) resistant viruses than parent nucleosides. The physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less activity against cell associated virus (EC50 = 91.9 mu M) when compared to 34 (EC50 = 0.8 mu M). Other conjugates showed less or comparable potency to that of the corresponding physical mixtures.

  DOI：

  10.1021/jm201551m

文献信息

• Synthesis and Anti-HIV Activities of Glutamate and Peptide Conjugates of Nucleoside Reverse Transcriptase Inhibitors
  作者：Hitesh K. Agarwal、Bhupender S. Chhikara、Megrose Quiterio、Gustavo F. Doncel、Keykavous Parang

  DOI：10.1021/jm201551m

  日期：2012.3.22

  Mono-, di-, and trinucleoside conjugates of glutamate or peptide scaffolds containing nucleoside reverse transcriptase inhibitors were synthesized. Among dinucleoside glutamate ester derivatives, N-myristoylated derivatives showed significantly higher anti-HIV activity than the corresponding N-acetylated conjugates against cell-free virus. Myristoyl-Glu(3TC)-FLT (46, EC50 = 0.3-0.6 mu M) and myristoyl-Glu(FTC)-FLT (47, EC50 = 0.1-0.4 mu M) derivatives were the most active glutamate-dinucleoside conjugates. A trinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC50 = 0.9-1.4 mu M) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus. Compound 34 also exhibited higher anti-HIV activity against multidrug (IC50 = 5.9 nM) and NNRTI (IC50 = 12.9 nM) resistant viruses than parent nucleosides. The physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less activity against cell associated virus (EC50 = 91.9 mu M) when compared to 34 (EC50 = 0.8 mu M). Other conjugates showed less or comparable potency to that of the corresponding physical mixtures.
• N-Myristoylglutamic acid derivative of 3′-fluoro-3′-deoxythymidine as an organogel
  作者：Bhupender S. Chhikara、Rakesh Tiwari、Keykavous Parang

  DOI：10.1016/j.tetlet.2012.07.101

  日期：2012.9

  Designing microbicidal gels of anti-HIV drugs for local application to prevent HIV infection is a subject of major interest. 3'-Fluoro-3'-deoxythymidine (FLT), a nucleoside reverse transcriptase inhibitor (NRTI), was conjugated with a N-myristoylglutamate scaffold. The conjugate showed gelation at 1% (w/w) in different organic solvents, such as toluene, dichloromethane, and chloroform. The gels were opaque and stable at room temperature. The results indicate that myristoyl glutamate derivative of FLT can form an organogel. The gel could have potential application as a topical anti-HIV microbicidal agent. (c) 2012 Elsevier Ltd. All rights reserved.