4-((3-(pyrrolidin-1-yl)propyl)amino)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-((3-(pyrrolidin-1-yl)propyl)amino)naphthalene-1,2-dione
• 英文别名: 4-(3-Pyrrolidin-1-ylpropylamino)naphthalene-1,2-dione；4-(3-pyrrolidin-1-ylpropylamino)naphthalene-1,2-dione
• 化学式: C₁₇H₂₀N₂O₂
• 分子量: 284.358
• InChiKey: BFDAKVLPROGVKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  4

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-((3-(pyrrolidin-1-yl)propyl)amino)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

• 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.