QL-X-138 | 1469988-63-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: QL-X-138
• 英文别名: N-[2-methyl-5-[2-oxo-9-(1H-pyrazol-4-yl)-1-benzo[h][1,6]naphthyridinyl]phenyl]-2-propenamide；N-[2-methyl-5-[2-oxo-9-(1H-pyrazol-4-yl)benzo[h][1,6]naphthyridin-1-yl]phenyl]prop-2-enamide
• CAS: 1469988-63-3
• 化学式: C₂₅H₁₉N₅O₂
• 分子量: 421.458
• InChiKey: JMVDIGHUQAXWIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-methyl-3-nitrophenyl)-9-(1H-pyrazol-4-yl)benzo[h][1,6]naphthyridin-2-one 在 tin(II) chloride dihdyrate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 QL-X-138
  参考文献：
  名称：

  Structure–Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent

  摘要：

  Here we report the structure activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum antiviral activity against dengue virus and other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent BTK inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation.

  DOI：

  10.1021/acsmedchemlett.7b00008

文献信息

• Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10000483B2

  公开（公告）日：2018-06-19

  The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I) or (II), or compositions thereof, for treating or preventing a wide range of diseases (e.g., proliferative diseases (e.g., cancers, benign neoplasms, angiogenesis, inflammatory diseases, autoimmune diseases) and metabolic diseases (e.g., diabetes (e.g., type 2 diabetes, gestational diabetes)) in a subject. Treatment of a subject with a disease using a compound of Formula (I) or (II), or compositions thereof, may downregulate the expression and/or inhibit the activity of a kinase (e.g., a tyrosine kinase, such as a Tec kinase, in particular, bone marrow on X chromosome kinase (BMX)), and therefore, suppress tyrosine kinase singling in the subject.

  本发明提供了新颖的式(I)化合物及其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同系物、立体异构体、同位素标记的衍生物、原药及其组合物。还提供了涉及式（I）或（II）化合物或其组合物的方法和试剂盒，用于治疗或预防受试者的多种疾病（如增殖性疾病（如癌症、良性肿瘤、血管生成、炎症性疾病、自身免疫性疾病）和代谢性疾病（如糖尿病（如 2 型糖尿病、妊娠糖尿病））。使用式(I)或(II)化合物或其组合物治疗患有疾病的受试者，可下调激酶（如酪氨酸激酶，如Tec激酶，特别是X染色体上的骨髓激酶（BMX））的表达和/或抑制其活性，从而抑制受试者体内的酪氨酸激酶单体。
• BONE MARROW ON X CHROMOSOME KINASE (BMX) INHIBITORS AND USES THEREOF
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20150246913A1

  公开（公告）日：2015-09-03

  The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I) or (II), or compositions thereof, for treating or preventing a wide range of diseases (e.g., proliferative diseases (e.g., cancers, benign neoplasms, angiogenesis, inflammatory diseases, autoimmune diseases) and metabolic diseases (e.g., diabetes (e.g., type 2 diabetes, gestational diabetes)) in a subject. Treatment of a subject with a disease using a compound of Formula (I) or (II), or compositions thereof, may downregulate the expression and/or inhibit the activity of a kinase (e.g., a tyrosine kinase, such as a Tec kinase, in particular, bone marrow on X chromosome kinase (BMX)), and therefore, suppress tyrosine kinase singling in the subject.
• HOST TARGETED INHIBITORS OF DENGUE VIRUS AND OTHER VIRUSES
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20190292178A9

  公开（公告）日：2019-09-26

  Novel antiviral compounds of Formulae (I)-(III) are provided: The inventive compounds, pharmaceutical compositions thereof, and kits including the inventive compounds are useful for the prevention and treatment of infectious diseases caused by viruses, for example, by Flaviviridae virus (e.g., Dengue virus (DENV)), Kunjin virus, Japanese encephalitis virus, vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), human cytomegalovirus (HCMV), poliovirus, Junin virus, Ebola virus, Marburg virus (MARV), Lassa fever virus (LASV), Venezuelan equine encephalitis virus (VEEV), or Rift Valley Fever virus (RVFV).