benzyl (2R)-5-[[5-(2-amino-5-oxo-1,4-dihydroimidazol-4-yl)-1-oxo-1-phenylmethoxypentan-2-yl]amino]-2-(dodecanoylamino)-5-oxopentanoate | 1269619-71-7

• 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: benzyl (2R)-5-[[5-(2-amino-5-oxo-1,4-dihydroimidazol-4-yl)-1-oxo-1-phenylmethoxypentan-2-yl]amino]-2-(dodecanoylamino)-5-oxopentanoate
• CAS: 1269619-71-7
• 化学式: C₃₉H₅₅N₅O₇
• 分子量: 705.895
• InChiKey: LIQIBNDKYZYQOD-OXLCSVRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  51
• 可旋转键数：
  27
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl (2R)-5-[[5-(2-amino-5-oxo-1,4-dihydroimidazol-4-yl)-1-oxo-1-phenylmethoxypentan-2-yl]amino]-2-(dodecanoylamino)-5-oxopentanoate 在 20 % Pd(OH)2/C 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以38 mg的产率得到(2R)-5-((4-(2-amino-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-1-carboxybutyl)amino)-2-dodecanamido-5-oxopentanoic acid
  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 7.5h， 生成 benzyl (2R)-5-[[5-(2-amino-5-oxo-1,4-dihydroimidazol-4-yl)-1-oxo-1-phenylmethoxypentan-2-yl]amino]-2-(dodecanoylamino)-5-oxopentanoate
  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