methyl 4-amino-3-((tert-butoxycarbonyl)amino)benzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-amino-3-((tert-butoxycarbonyl)amino)benzoate
• 英文别名: Methyl 4-amino-3-((tert-butoxycarbonyl)amino)benzoate；methyl 4-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]benzoate
• 化学式: C₁₃H₁₈N₂O₄
• 分子量: 266.297
• InChiKey: LUCNNIGCGMKFPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-amino-3-((tert-butoxycarbonyl)amino)benzoate 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-methyl 2-(3,4-diaminobenzamido)-5-guanidinopentanoate
  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
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 3,4-二氨基苯甲酸甲酯 在 盐酸胍 作用下， 以 乙醇 为溶剂， 反应 0.67h， 以83%的产率得到methyl 4-amino-3-((tert-butoxycarbonyl)amino)benzoate
  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

• Structure-Based Design of Xanthine-Benzimidazole Derivatives as Novel and Potent Tryptophan Hydroxylase Inhibitors
  作者：Edgar Specker、Susann Matthes、Radoslaw Wesolowski、Anja Schütz、Maik Grohmann、Natalia Alenina、Dirk Pleimes、Keven Mallow、Martin Neuenschwander、Angelina Gogolin、Marie Weise、Jochen Pfeifer、Nandor Ziebart、Udo Heinemann、Jens Peter von Kries、Marc Nazaré、Michael Bader

  DOI：10.1021/acs.jmedchem.2c00598

  日期：2022.8.25

  this disease. Here, we describe a novel class of potent tryptophan hydroxylase inhibitors, characterized by spanning all active binding sites important for catalysis, specifically those of the cosubstrate pterin, the substrate tryptophan as well as directly chelating the catalytic iron ion. The inhibitors were designed to efficiently reduce serotonin in the periphery while not passing the blood–brain

  色氨酸羟化酶催化血清素合成的第一步和限速步骤。5-羟色胺是中枢神经系统中的一种关键神经递质，在外周，作为具有多种生理功能的局部激素发挥作用。对转基因小鼠模型的研究表明，外周血清素水平的失调会导致代谢、炎症和纤维化疾病。肿瘤细胞过度产生血清素会导致类癌综合征典型的严重症状，色氨酸羟化酶抑制剂已经在临床上用于患有这种疾病的患者。在这里，我们描述了一类新的强效色氨酸羟化酶抑制剂，其特征在于跨越所有对催化重要的活性结合位点，特别是那些共底物蝶呤，底物色氨酸以及直接螯合催化铁离子。这些抑制剂旨在有效减少外周的血清素，同时不通过血脑屏障，从而保持大脑中的血清素水平。