(S)-methyl 2-(3-amino-4-((S)-2-amino-3-(4-hydroxyphenyl)propanamido)benzamido)-3-(4-hydroxyphenyl)propanoate

• 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)-methyl 2-(3-amino-4-((S)-2-amino-3-(4-hydroxyphenyl)propanamido)benzamido)-3-(4-hydroxyphenyl)propanoate
• 英文别名: methyl (2S)-2-[[3-amino-4-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]benzoyl]amino]-3-(4-hydroxyphenyl)propanoate
• 化学式: C₂₆H₂₈N₄O₆
• 分子量: 492.532
• InChiKey: MMHWDEYTWTZRBI-GMAHTHKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  177
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,4-二氨基苯甲酸甲酯 在 盐酸胍 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 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 0.67h， 生成 (S)-methyl 2-(3-amino-4-((S)-2-amino-3-(4-hydroxyphenyl)propanamido)benzamido)-3-(4-hydroxyphenyl)propanoate
  参考文献：
  名称：

  3,4-Diaminobenzoic Acid Derivatives as Inhibitors of the Oxytocinase Subfamily of M1 Aminopeptidases with Immune-Regulating Properties

  摘要：

  Members of the oxytocinase subfamily of M1 aminopeptidases (ERAP1, ERAP2, and IRAP) play important roles in both the adaptive and innate human immune responses. Their enzymatic activity can contribute to the pathogenesis of several major human diseases ranging from viral and parasitic infections to autoimmunity and cancer. We have previously demonstrated that diaminobenzoic acid derivatives show promise as selective inhibitors for this group of aminopeptidases. In this study, we have thoroughly explored a series of 3,4-diaminobenzoic acid derivatives as inhibitors of this class of enzymes, achieving submicromolar inhibitors for ERAP2 (IC50 = 237 nM) and IRAP (IC50 = 105 nM). Cell-based analysis indicated that the lead compounds can be effective in downregulating macrophage activation induced by lipopolysaccharide and interferon-gamma as well as cross-presentation by bone marrow-derived dendritic cells. Our results indicate that this class of inhibitors may be useful for the targeted downregulation of immune responses.

  DOI：

  10.1021/jm501867s

文献信息

• 3,4-Diaminobenzoic Acid Derivatives as Inhibitors of the Oxytocinase Subfamily of M1 Aminopeptidases with Immune-Regulating Properties
  作者：Athanasios Papakyriakou、Efthalia Zervoudi、Sofia Tsoukalidou、Francois-Xavier Mauvais、Georgia Sfyroera、Dimitrios C. Mastellos、Peter van Endert、Emmanuel A. Theodorakis、Dionisios Vourloumis、Efstratios Stratikos

  DOI：10.1021/jm501867s

  日期：2015.2.12

  Members of the oxytocinase subfamily of M1 aminopeptidases (ERAP1, ERAP2, and IRAP) play important roles in both the adaptive and innate human immune responses. Their enzymatic activity can contribute to the pathogenesis of several major human diseases ranging from viral and parasitic infections to autoimmunity and cancer. We have previously demonstrated that diaminobenzoic acid derivatives show promise as selective inhibitors for this group of aminopeptidases. In this study, we have thoroughly explored a series of 3,4-diaminobenzoic acid derivatives as inhibitors of this class of enzymes, achieving submicromolar inhibitors for ERAP2 (IC50 = 237 nM) and IRAP (IC50 = 105 nM). Cell-based analysis indicated that the lead compounds can be effective in downregulating macrophage activation induced by lipopolysaccharide and interferon-gamma as well as cross-presentation by bone marrow-derived dendritic cells. Our results indicate that this class of inhibitors may be useful for the targeted downregulation of immune responses.