4-((2-(dimethylamino)ethyl)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-((2-(dimethylamino)ethyl)amino)naphthalene-1,2-dione
• 英文别名: 4-[2-(Dimethylamino)ethylamino]naphthalene-1,2-dione
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: RQEGNESJMYQOJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 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-((2-(dimethylamino)ethyl)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

• NOVEL ORTHO-NAPHTHOQUINONE DERIVATIVES, NOVEL SYNTHESIS THEREFOR, AND THEIR USE IN THE INHIBITION OF NEOPLASTIC CELL GROWTH
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：EP0888326A2

  公开（公告）日：1999-01-07
• US5883270A
  申请人：——

  公开号：US5883270A

  公开（公告）日：1999-03-16
• US5977187A
  申请人：——

  公开号：US5977187A

  公开（公告）日：1999-11-02
• US7253207B2
  申请人：——

  公开号：US7253207B2

  公开（公告）日：2007-08-07
• [EN] NOVEL ORTHO-NAPHTHOQUINONE DERIVATIVES, NOVEL SYNTHESIS THEREFOR, AND THEIR USE IN THE INHIBITION OF NEOPLASTIC CELL GROWTH<br/>[FR] NOUVEAUX DERIVES D'ORTHO-NAPHTHOQUINONE, PROCEDE DE SYNTHESE CORRESPONDANT ET UTILISATION DE CES DERIVES POUR INHIBER LA CROISSANCE CELLULAIRE NEOPLASIQUE
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：WO1997031936A2

  公开（公告）日：1997-09-04

  (EN) A novel synthetic method, novel compounds formed using the synthetic method, and uses for the compounds so made are described. The synthetic method results in the formation of $i(o)-naphthoquinone derivatives. These compounds find use as potent inhibitors of neoplastic cell growth and proliferation.(FR) Cette invention concerne un nouveau procédé de synthèse, de nouveaux composés obtenus par ce procédé de synthèse ainsi que des utilisations de ces composés. Ledit procédé de synthèse aboutit à la formation de dérivés d'$i(ortho)-naphthoquinone. Ces composés s'avèrent utiles en tant qu'inhibiteurs de la croissance et de la prolifération cellulaire néoplasique.