2-hydroxy-6,7-dimethoxy-3-(3-methylbut-2-en-1-yl)-naphthalene-1,4-dione | 90149-81-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮
• 英文名称: 2-hydroxy-6,7-dimethoxy-3-(3-methylbut-2-en-1-yl)-naphthalene-1,4-dione
• CAS: 90149-81-8
• 化学式: C₁₇H₁₈O₅
• 分子量: 302.327
• InChiKey: GGTIJLOFSPMOPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.83
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-6,7-dimethoxy-3-(3-methylbut-2-en-1-yl)-naphthalene-1,4-dione 在 硫酸 作用下， 反应 0.25h， 以78%的产率得到8,9-dimethoxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]-chromene-5,6-dione
  参考文献：
  名称：

  .beta.-Lapachone: synthesis of derivatives and activities in tumor models

  摘要：

  In order to find a 3,4-dihydro-2H-naphtho[1,2-b]pyran-5,6-dione more potent than the naturally occurring 2,2-dimethyl derivative [beta-lapachone (10a)], we synthesized a series of analogous compounds with modifications at position 2 of the pyran ring or at positions 8 and 9 of the benzene ring. Of the compounds tested in vitro for inhibition of RNA-dependent DNA polymerase and in mice infected with Rauscher leukemia, all retained good enzyme activity. Inhibition of the reverse transcriptase activity of the 2,2-substituted derivatives 10b-e was as strong as 10a. However, only the 2-methyl-2-phenyl derivative 10e proved to be about as potent as the 2,2-dimethyl reference compound 10a in prolonging the mean survival time of mice with Rauscher leukemia virus induced leukemia.

  DOI：

  10.1021/jm00374a010
• 作为产物：
  描述：

  6,7-二甲氧基-3,4-二氢-2H-1-萘酮 在 potassium tert-butylate 、 氧气 、 lithium hydride 作用下， 以 二甲基亚砜 、 叔丁醇 为溶剂， 反应 13.5h， 生成 2-hydroxy-6,7-dimethoxy-3-(3-methylbut-2-en-1-yl)-naphthalene-1,4-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