(6R)-11,15-dibenzyl 6-undecyl2,2,19,19-tetramethyl-4,9,17-trioxo-3,18-dioxa-5,10,16-triazaicosane-6,11,15-tricarboxylate | 1269619-76-2

• 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: (6R)-11,15-dibenzyl 6-undecyl2,2,19,19-tetramethyl-4,9,17-trioxo-3,18-dioxa-5,10,16-triazaicosane-6,11,15-tricarboxylate
• 英文别名: dibenzyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-6-[[(4R)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-5-undecoxypentanoyl]amino]heptanedioate
• CAS: 1269619-76-2
• 化学式: C₄₇H₇₁N₃O₁₁
• 分子量: 854.094
• InChiKey: QAIAOLOHVLAQCM-DFCGPKRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  61
• 可旋转键数：
  34
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  185
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (6R)-11,15-dibenzyl 6-undecyl2,2,19,19-tetramethyl-4,9,17-trioxo-3,18-dioxa-5,10,16-triazaicosane-6,11,15-tricarboxylate 在 20 % Pd(OH)2/C 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成
  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：

  BOC-D-谷氨酸5-叔丁酯 在 哌啶 、 4-二甲氨基吡啶 、 Wilkinson's catalyst 、 sodium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.25h， 生成 (6R)-11,15-dibenzyl 6-undecyl2,2,19,19-tetramethyl-4,9,17-trioxo-3,18-dioxa-5,10,16-triazaicosane-6,11,15-tricarboxylate
  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