N-(3-aminopropyl)-N-(4-azido-2,5-dimethoxyphenyl)-4-ethoxybenzenesulfonamide

• 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: N-(3-aminopropyl)-N-(4-azido-2,5-dimethoxyphenyl)-4-ethoxybenzenesulfonamide
• 化学式: C₁₉H₂₅N₅O₅S
• 分子量: 435.504
• InChiKey: PJZKFRBOPOQSLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(3-aminopropyl)-N-(4-azido-2,5-dimethoxyphenyl)-4-ethoxybenzenesulfonamide 、 D-生物素 在 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以67%的产率得到N-(3-((N-(4-azido-2_,5-dimethoxyphenyl)-4-ethoxyphenyl)sulfonamido) propyl)-5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide
  参考文献：
  名称：

  [EN] N-ARYL SULFONAMIDE DERIVATIVES AS VACCINE ADJUVANT
  [FR] DÉRIVÉS DE N-ARYLSULFONAMIDE EN TANT QU'ADJUVANT VACCINAL

  摘要：

  提供双芳基磺酰胺化合物及使用这些化合物的方法，例如，在增强或延长免疫反应的方法中使用。例如，这些化合物可以与疫苗一起使用，可选择性地至少一个其他佐剂和/或一个或多个TLR配体，至少一个MAP激酶抑制剂，或任意组合。

  公开号：

  WO2021034729A1
• 作为产物：
  描述：

  2,5-二甲氧基-4-硝基苯胺 在 盐酸 、 亚硝酸特丁酯 、 叠氮基三甲基硅烷 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 sodium sulfate 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~45.0 ℃ 、344.75 kPa 条件下， 反应 10.0h， 生成 N-(3-aminopropyl)-N-(4-azido-2,5-dimethoxyphenyl)-4-ethoxybenzenesulfonamide
  参考文献：
  名称：

  Structure–Activity Relationship Studies To Identify Affinity Probes in Bis-aryl Sulfonamides That Prolong Immune Stimuli

  摘要：

  Agents that safely induce, enhance, or sustain multiple innate immune signaling pathways could be developed as potent vaccine adjuvants or coadjuvants. Using high-X throughput screens with cell-based nuclear factor kappa B (NF-kappa B) and interferon stimulating response element (ISRE) reporter assays, we identified a bis-aryl sulfonamide bearing compound 1 that demonstrated sustained NF-kappa B and ISRE activation after a primary stimulus with lipopolysaccharide or interferon-alpha, respectively. Here, we present systematic structure-activity relationship (SAR) studies on the two phenyl rings and amide nitrogen of the sulfonamide group of compound 1 focused toward identification of affinity probes. The murine vaccination studies showed that compounds 1 and 33 when used as coadjuvants with monophosphoryl lipid A (MPLA) showed significant enhancement in antigen ovalbumin-specific immunoglobulin responses compared to MPLA alone. SAR studies pointed to the sites on the scaffold that can tolerate the introduction of aryl azide, biotin, and fluorescent rhodamine substituents to obtain several affinity and photoaffinity probes which will be utilized in concert for future target identification and mechanism of action studies.

  DOI：

  10.1021/acs.jmedchem.9b00870

文献信息

• Structure–Activity Relationship Studies To Identify Affinity Probes in Bis-aryl Sulfonamides That Prolong Immune Stimuli
  作者：Michael Chan、Fitzgerald S. Lao、Paul J. Chu、Jonathan Shpigelman、Shiyin Yao、Jason Nan、Fumi Sato-Kaneko、Vicky Li、Tomoko Hayashi、Maripat Corr、Dennis A. Carson、Howard B. Cottam、Nikunj M. Shukla

  DOI：10.1021/acs.jmedchem.9b00870

  日期：2019.11.14

  Agents that safely induce, enhance, or sustain multiple innate immune signaling pathways could be developed as potent vaccine adjuvants or coadjuvants. Using high-X throughput screens with cell-based nuclear factor kappa B (NF-kappa B) and interferon stimulating response element (ISRE) reporter assays, we identified a bis-aryl sulfonamide bearing compound 1 that demonstrated sustained NF-kappa B and ISRE activation after a primary stimulus with lipopolysaccharide or interferon-alpha, respectively. Here, we present systematic structure-activity relationship (SAR) studies on the two phenyl rings and amide nitrogen of the sulfonamide group of compound 1 focused toward identification of affinity probes. The murine vaccination studies showed that compounds 1 and 33 when used as coadjuvants with monophosphoryl lipid A (MPLA) showed significant enhancement in antigen ovalbumin-specific immunoglobulin responses compared to MPLA alone. SAR studies pointed to the sites on the scaffold that can tolerate the introduction of aryl azide, biotin, and fluorescent rhodamine substituents to obtain several affinity and photoaffinity probes which will be utilized in concert for future target identification and mechanism of action studies.
• [EN] N-ARYL SULFONAMIDE DERIVATIVES AS VACCINE ADJUVANT<br/>[FR] DÉRIVÉS DE N-ARYLSULFONAMIDE EN TANT QU'ADJUVANT VACCINAL
  申请人：UNIV CALIFORNIA

  公开号：WO2021034729A1

  公开（公告）日：2021-02-25

  Bis-aryl sulfonamide compounds and methods of using those compounds, e.g., in a method of enhancing or prolonging an immune response, are provided. For example, the compounds may be employed with a vaccine and optionally at least one other adjuvant and/or one or more TLR ligands, at least one MAP kinase inhibitor, or any combination thereof.

  提供双芳基磺酰胺化合物及使用这些化合物的方法，例如，在增强或延长免疫反应的方法中使用。例如，这些化合物可以与疫苗一起使用，可选择性地至少一个其他佐剂和/或一个或多个TLR配体，至少一个MAP激酶抑制剂，或任意组合。