dibenzyl 2-amino-6-((R)-5-(benzyloxy)-4-dodecanamido-5-oxopentanamido)heptanedioate | 1269619-60-4

• 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: dibenzyl 2-amino-6-((R)-5-(benzyloxy)-4-dodecanamido-5-oxopentanamido)heptanedioate
• 英文别名: dibenzyl 2-amino-6-[[(4R)-4-(dodecanoylamino)-5-oxo-5-phenylmethoxypentanoyl]amino]heptanedioate
• CAS: 1269619-60-4
• 化学式: C₄₅H₆₁N₃O₈
• 分子量: 771.995
• InChiKey: UBGMOVMWADQMQT-QJTYWPRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  56
• 可旋转键数：
  31
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  dibenzyl 2-amino-6-((R)-5-(benzyloxy)-4-dodecanamido-5-oxopentanamido)heptanedioate 在 吡啶 、 20 % Pd(OH)2/C 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 50.0 ℃ 、413.7 kPa 条件下， 反应 4.5h， 生成 2-((R)-4-carboxy-4-dodecanamidobutanamido)-6-guanidinoheptanedioic acid trifluoroacetate
  参考文献：
  名称：

  Structure−Activity Relationships in Nucleotide Oligomerization Domain 1 (Nod1) Agonistic γ-Glutamyldiaminopimelic Acid Derivatives

  摘要：

  N-Acyl-gamma-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C-12-gamma-D-Glu-DAP. Analogues with glutaric or gamma-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopirnelic acid, L- or D-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the D-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic but active analogues. Transcriptomal profiling showed a dominant up-regulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1 and TLR agonists and are likely to be useful in designing vaccine adjuvants.

  DOI：

  10.1021/jm101535e
• 作为产物：
  描述：

  dibenzyl 2-((R)-4-amino-5-(benzyloxy)-5-oxopentanamido)-6-((tert-butoxycarbonyl)amino)heptanedioate 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 6.5h， 生成 dibenzyl 2-amino-6-((R)-5-(benzyloxy)-4-dodecanamido-5-oxopentanamido)heptanedioate
  参考文献：
  名称：

  Structure−Activity Relationships in Nucleotide Oligomerization Domain 1 (Nod1) Agonistic γ-Glutamyldiaminopimelic Acid Derivatives

  摘要：

  N-Acyl-gamma-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C-12-gamma-D-Glu-DAP. Analogues with glutaric or gamma-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity. Substitution of the meso-diaminopimelic (DAP) acid component with monoaminopirnelic acid, L- or D-lysine, or cadaverine also results in reduced activity. The free amine on DAP is crucial. However, the N-acyl group on the D-glutamyl residue can be substituted with N-alkyl groups with full preservation of activity. The free carboxylates on the DAP and Glu components can also be esterified, resulting in more lipophilic but active analogues. Transcriptomal profiling showed a dominant up-regulation of IL-19, IL-20, IL-22, and IL-24, which may explain the pronounced Th2-polarizing activity of these compounds and also implicate cell signaling mediated by TREM-1. These results may explain the hitherto unknown mechanism of synergy between Nod1 and TLR agonists and are likely to be useful in designing vaccine adjuvants.

  DOI：

  10.1021/jm101535e