(S)-2-amino-6-((R)-4-carboxy-4-dodecanamidobutanamido)hexanoic acid trifluoroacetate | 1269620-51-0

• 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: (S)-2-amino-6-((R)-4-carboxy-4-dodecanamidobutanamido)hexanoic acid trifluoroacetate
• 英文别名: H-Lys(1)-OH.lauroyl-D-Glu(1)-OH.TFA；(2S)-2-amino-6-[[(4R)-4-carboxy-4-(dodecanoylamino)butanoyl]amino]hexanoic acid;2,2,2-trifluoroacetic acid
• CAS: 1269620-51-0
• 化学式: C₂HF₃O₂*C₂₃H₄₃N₃O₆
• 分子量: 571.635
• InChiKey: WYPONKLNVWFAQM-GRTNUQQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  39
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  196
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  BOC-D-谷氨酸5-叔丁酯 在 哌啶 、 吡啶 、 4-二甲氨基吡啶 、 20 % Pd(OH)2/C 、 氢气 、 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 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 10.0~20.0 ℃ 、413.7 kPa 条件下， 反应 35.75h， 生成 (S)-2-amino-6-((R)-4-carboxy-4-dodecanamidobutanamido)hexanoic 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

文献信息

• Structure−Activity Relationships in Nucleotide Oligomerization Domain 1 (Nod1) Agonistic γ-Glutamyldiaminopimelic Acid Derivatives
  作者：Geetanjali Agnihotri、Rehman Ukani、Subbalakshmi S. Malladi、Hemamali J. Warshakoon、Rajalakshmi Balakrishna、Xinkun Wang、Sunil A. David

  DOI：10.1021/jm101535e

  日期：2011.3.10

  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.