1-[（2-苯乙基）氨基]-3H-萘[1,2,3-de]喹啉-2,7-二酮 | 376382-11-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 中文名称: 1-[（2-苯乙基）氨基]-3H-萘[1,2,3-de]喹啉-2,7-二酮
• 英文名称: BRD7389
• 英文别名: 1-(Phenethylamino)-3H-naphtho[1,2,3-de]quinoline-2,7-dione；16-(2-phenylethylamino)-14-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2,4,6,9(17),10,12-heptaene-8,15-dione
• CAS: 376382-11-5
• 化学式: C₂₄H₁₈N₂O₂
• 分子量: 366.419
• InChiKey: XASCINRGTHLHGM-UHFFFAOYSA-N

物化性质

• 沸点：
  655.0±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

制备方法与用途

生物活性

BRD7389 是一种特异性的 RSK 家族激酶抑制剂，对 RSK1、RSK2 和 RSK3 的 IC50 分别为 1.5 μM、2.4 μM 和 1.2 μM。BRD7389 可以诱导胰腺 α 细胞中胰岛素表达。

靶点

• RSK1：1.5 μM (IC50)
• RSK2：2.4 μM (IC50)
• RSK3：1.2 μM (IC50)
• CDK5/p35：6.5 μM (IC50)
• DRAK1：2.8 μM (IC50)
• FLT3：3.5 μM (IC50)
• PIM1：3.7 μM (IC50)
• PKG1α：6.5 μM (IC50)
• SGK：13.8 μM (IC50)

体外研究

BRD7389 在 0.425 至 6.8 μM 浓度下，经过 3 天处理后可诱导小鼠 α 细胞中胰岛素的表达。在 0.85 μM 浓度时胰岛素（Ins2）mRNA 的上调达到峰值；经过 5 天处理后，BRD7389 对胰岛素基因表达的诱导效果增强，浓度为 0.85 μM 时可提高约 50 倍。

• RT-PCR

  • 细胞系：小鼠 α 细胞系
  • 浓度：0.425、0.85、1.7、3.4、6.8 μM
  • 孵育时间：3 天和 5 天
  • 结果：上调 Pdx1 的表达。

• 细胞增殖试验

  • 细胞系：SNU-407 结肠癌细胞
  • 浓度：1 μM
  • 孵育时间：在 Carbachol 治疗前 30 分钟加入 (48 小时)
  • 结果：几乎完全阻断了 Carbachol（1 mM）诱导的细胞增殖。

BRD7389 在添加 30 分钟后（48 小时），在浓度为 1 μM 的情况下，可完全抑制车巴奇醇 (Carbachol) 刺激下的细胞增殖，但对基底水平的增殖几乎没有影响。

反应信息

• 作为产物：
  描述：

  2-氯-N-(9,10-二氧代-9,10-二氢-1-蒽基)乙酰胺 在 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 1-[（2-苯乙基）氨基]-3H-萘[1,2,3-de]喹啉-2,7-二酮
  参考文献：
  名称：

  1-取代 3H-萘并[1,2,3-de]喹啉-2,7-二酮的合成

  摘要：

  摘要 一种N- (9,10-蒽醌-1-基)氯乙酰胺与对-钠反应制备1-甲苯磺酰-3H-萘并[1,2,3-脱]喹啉-2,7-二酮的方法开发了甲苯亚磺酸盐。已发现氮和氧亲核试剂对甲苯磺酰基的亲核取代在温和条件下进行。相应的 1-取代 3 H-萘并[1,2,3-脱]喹啉-2,7-二酮已通过这些化合物与胺、苯酚、氢氧化钠和叠氮化钠的反应获得。

  DOI：

  10.1134/s0012500822700112

文献信息

• Calmodulin inhibitors, Chk2 inhibitors and RSK inhibitors for the treatment of ribosomal disorders and ribosomapathies
  申请人：THE CHILDREN'S MEDICAL CENTER CORPORATION

  公开号：US10980808B2

  公开（公告）日：2021-04-20

  The present invention relates to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to the use of novel classes of compounds, i.e. inhibitors of RSK (p90S6K); inhibitors of p70S6K; and inhibitors of rps6, to treat ribosomal disorders and ribosomopathies. In some embodiments, the invention relates to the use of specific Chk2 inhibitors and to the use of specific phenothiazine derivatives to treat ribosomal disorders and ribosomopathies, e.g. DBA.

  本发明涉及治疗核糖体紊乱和核糖体病（如钻石黑凡贫血症（DBA））的方法、组合物和试剂盒。在一些实施方案中，本发明涉及使用新型化合物，即 RSK（p90S6K）的抑制剂；p70S6K 的抑制剂；和 rps6 的抑制剂，来治疗核糖体紊乱和核糖体病。在某些实施方案中，本发明涉及使用特异性 Chk2 抑制剂和特异性吩噻嗪衍生物治疗核糖体紊乱和核糖体病，如 DBA。
• CALMODULIN INHIBITORS, CHK2 INHIBITORS AND RSK INHIBITORS FOR THE TREATMENT OF RIBOSOMAL DISORDERS AND RIBOSOMAPATHIES
  申请人：THE CHILDREN'S MEDICAL CENTER CORPORATION

  公开号：US20190314374A1

  公开（公告）日：2019-10-17

  The present invention relates to methods, compositions and kits for treatment of ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to the use of novel classes of compounds, i.e. inhibitors of RSK (p90S6K); inhibitors of p70S6K; and inhibitors of rps6, to treat ribosomal disorders and ribosomopathies. In some embodiments, the invention relates to the use of specific Chk2 inhibitors and to the use of specific phenothiazine derivatives to treat ribosomal disorders and ribosomopathies, e.g. DBA.
• Phosphatase Binding Compounds and Methods of Using Same
  申请人：Yale University

  公开号：US20200268897A1

  公开（公告）日：2020-08-27

  The present invention provides bifunctional compounds that efficiently dephosphorylate certain phospho-activated target proteins. Such target proteins can be any protein involved in the pathway of a disease or disorder, such as but not limited to cancer, neurodegeneration, metabolic disease, diabetes, insulin resistance, and so forth.
• METHOD FOR PRODUCING INSULIN-PRODUCING CELLS
  申请人：KATAOKA CORPORATION

  公开号：US20210395689A1

  公开（公告）日：2021-12-23

  It is a main object of the present invention to provide a process for producing an insulin-producing cell from a somatic cell without performing artificial gene transfer, an insulin-producing cell obtained from the process, or a composition comprising a combination of chemical substances that can be used for the process. The present invention can include, for example: a process for producing an insulin-producing cell from a somatic cell by direct differentiation induction, comprising a step of culturing a somatic cell in the presence of an RSK inhibitor; an insulin-producing cell obtained from the process; and a composition for producing an insulin-producing cell from a somatic cell by directly inducing differentiation, comprising an RSK inhibitor. The insulin-producing cells obtained according to the present invention are useful in regenerative medicine and the like.
• METHOD FOR PRODUCING INSULIN-PRODUCING CELLS, AND COMPOSITION
  申请人：KATAOKA CORPORATION

  公开号：US20220025336A1

  公开（公告）日：2022-01-27

  It is a main object of the present invention to provide a new producing method capable of efficiently performing direct conversion or induction from a somatic cell to an insulin-producing cell. The present invention can include, for example, a process for producing an insulin-producing cell by direct differentiation induction from a somatic cell, comprising a step of culturing a somatic cell in a serum-free differentiation induction medium, or a step of culturing a somatic cell in a differentiation induction medium containing 5 μg/mL or more of insulin. According to the present invention, insulin-producing cells having a high insulin secretion ability can be produced directly and efficiently from a somatic cell. The insulin-producing cells obtained according to the present invention are useful in regenerative medicine and the like.