methyl (2S)-3-(1H-indol-3-yl)-2-[[4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-6-[[2,4,6-triethyl-3,5-bis[[[6-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-1,3,5-triazin-2-yl]amino]methyl]phenyl]methylamino]-1,3,5-triazin-2-yl]amino]propanoate | 1316666-29-1

• 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: methyl (2S)-3-(1H-indol-3-yl)-2-[[4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-6-[[2,4,6-triethyl-3,5-bis[[[6-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-1,3,5-triazin-2-yl]amino]methyl]phenyl]methylamino]-1,3,5-triazin-2-yl]amino]propanoate
• CAS: 1316666-29-1
• 化学式: C₉₆H₁₀₂N₂₄O₁₂
• 分子量: 1784.02
• InChiKey: GFGHKOROYSPNCN-AROKCNTCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  18
• 重原子数：
  132
• 可旋转键数：
  48
• 环数：
  16.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  477
• 氢给体数：
  15
• 氢受体数：
  30

反应信息

• 作为反应物：
  描述：

  methyl (2S)-3-(1H-indol-3-yl)-2-[[4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-6-[[2,4,6-triethyl-3,5-bis[[[6-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-1,3,5-triazin-2-yl]amino]methyl]phenyl]methylamino]-1,3,5-triazin-2-yl]amino]propanoate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以86%的产率得到(2S)-2-[[4-[[3,5-bis[[[6-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-4-[[(1R)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1,3,5-triazin-2-yl]amino]methyl]-2,4,6-triethylphenyl]methylamino]-6-[[(1R)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-1,3,5-triazin-2-yl]amino]-3-(1H-indol-3-yl)propanoic acid
  参考文献：
  名称：

  Targeting HIV Entry through Interaction with Envelope Glycoprotein 120 (gp120): Synthesis and Antiviral Evaluation of 1,3,5-Triazines with Aromatic Amino Acids

  摘要：

  On the basis of the interesting inhibitory properties that lectins show against HIV-replication through their interaction with glycoprotein 120 (gp120), we here describe the design, synthesis, and anti-HIV evaluation of three series of 1,3,5-triazine derivatives (monomers, dimers, and trimers) functionalized with aromatic amino acids meant to mimic interactions that lectins establish with gp120. While monomers were inactive against HIV replication, dimers showed limited anti-HIV activity that is, however, considerably more significant in the trimers series, with EC(50) values in the lower mu M range. These findings most likely reflect the requirement of multivalency of the 1,3,5-triazine derivatives to display anti-HIV activity, as lectins do. The pronounced anti-HIV activity (EC(50) similar to 20 mu M) is accompanied by the absence of toxicity in CEM T-cell line (CC(50) > 250 mu M). Moreover, SPR experiments revealed that the prototype trimers with a central core of 2,4,6-triethylbenzene and six L-Trp or six L-Tyr residues at the periphery were efficient binders of CXCR4- and CCR5-tropic HIV-1 gp120 (estimated K(D): lower micromolar range). The collected data support the interest of this novel family of anti-HIV agents and qualify them as potential novel microbicide lead compounds.

  DOI：

  10.1021/jm200560r
• 作为产物：
  描述：

  methyl (2R)-2-[[4-chloro-6-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-1,3,5-triazin-2-yl]amino]-3-(1H-indol-3-yl)propanoate 、 1,3,5-三(氨基甲基)-2,4,6-三乙基苯 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以34%的产率得到methyl (2S)-3-(1H-indol-3-yl)-2-[[4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-6-[[2,4,6-triethyl-3,5-bis[[[6-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-4-[[(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]amino]-1,3,5-triazin-2-yl]amino]methyl]phenyl]methylamino]-1,3,5-triazin-2-yl]amino]propanoate
  参考文献：
  名称：

  Targeting HIV Entry through Interaction with Envelope Glycoprotein 120 (gp120): Synthesis and Antiviral Evaluation of 1,3,5-Triazines with Aromatic Amino Acids

  摘要：

  On the basis of the interesting inhibitory properties that lectins show against HIV-replication through their interaction with glycoprotein 120 (gp120), we here describe the design, synthesis, and anti-HIV evaluation of three series of 1,3,5-triazine derivatives (monomers, dimers, and trimers) functionalized with aromatic amino acids meant to mimic interactions that lectins establish with gp120. While monomers were inactive against HIV replication, dimers showed limited anti-HIV activity that is, however, considerably more significant in the trimers series, with EC(50) values in the lower mu M range. These findings most likely reflect the requirement of multivalency of the 1,3,5-triazine derivatives to display anti-HIV activity, as lectins do. The pronounced anti-HIV activity (EC(50) similar to 20 mu M) is accompanied by the absence of toxicity in CEM T-cell line (CC(50) > 250 mu M). Moreover, SPR experiments revealed that the prototype trimers with a central core of 2,4,6-triethylbenzene and six L-Trp or six L-Tyr residues at the periphery were efficient binders of CXCR4- and CCR5-tropic HIV-1 gp120 (estimated K(D): lower micromolar range). The collected data support the interest of this novel family of anti-HIV agents and qualify them as potential novel microbicide lead compounds.

  DOI：

  10.1021/jm200560r