4-(phenethylamino)naphthalene-1,2-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(phenethylamino)naphthalene-1,2-dione
• 英文别名: 4-(2-phenylethylamino)naphthalene-1,2-dione
• 化学式: C₁₈H₁₅NO₂
• 分子量: 277.323
• InChiKey: CWFAFDYCTDBGBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,2-萘醌 在 sodium iodate 、 cerium(III) chloride heptahydrate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 4-(phenethylamino)naphthalene-1,2-dione
  参考文献：
  名称：

  Identification of β-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma

  摘要：

  The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar beta-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and, beta-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure activity relationships by incorporating electron-withdrawing substituents at C8 position of beta-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1.

  DOI：

  10.1021/acs.jmedchem.5b01415

文献信息

• On-Line Derivatization into Precolumns for the Determination of Drugs by Liquid Chromatography and Column Switching:  Determination of Amphetamines in Urine
  作者：Rosa Herráez-Hernández、Pilar Campíns-Falcó、Adela Sevillano-Cabeza

  DOI：10.1021/ac9505076

  日期：1996.3.1

  A chromatographic system for the on-line derivatization of drugs using column switching is described. The system uses a 20 mm x 2.1 mm i.d. precolumn packed with a unmodified ODS stationary phase. This column is used for sample cleanup and enrichment of the analytes. Next, the trapped analytes are derivatized by injection of the derivatization reagent into the precolumn. Finally, the derivatives are

  描述了一种使用柱切换进行药物在线衍生化的色谱系统。该系统使用内径为20 mm x 2.1 mm的预柱，其中填充了未经修饰的ODS固定相。该柱用于样品净化和分析物富集。接下来，通过将衍生化试剂注入到预柱中来对捕获的分析物进行衍生化。最后，将衍生物转移到分析柱中以在反相条件下进行分离。已研究了一些参数（例如反应时间，衍生化试剂的量或系统设计）的影响，其中一些苯丙胺作为模型化合物，还研究了三种衍生化试剂：1、2，2-萘醌-4-磺酸钠，邻苯二甲醛和9-芴基甲基氯甲酸酯。
• NAKAHARA, Y.;TAKEDA, Y., CHROMATOGRAPHIA, 26,(1988) C. 363-368
  作者：NAKAHARA, Y.、TAKEDA, Y.

  DOI：——

  日期：——
• Identification of β-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma
  作者：Sang Min Lim、Yujeong Jeong、Suhyun Lee、Honggu Im、Hyun Seop Tae、Byung Gyu Kim、Hee Dong Park、Jonghoon Park、Sungwoo Hong

  DOI：10.1021/acs.jmedchem.5b01415

  日期：2015.11.12

  The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar beta-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and, beta-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure activity relationships by incorporating electron-withdrawing substituents at C8 position of beta-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1.