1-(3-Amino-4-methylphenyl)-9-(6-aminopyridin-3-yl)benzo[h][1,6]naphthyridin-2-one | 1223001-82-8

• 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: 1-(3-Amino-4-methylphenyl)-9-(6-aminopyridin-3-yl)benzo[h][1,6]naphthyridin-2-one
• CAS: 1223001-82-8
• 化学式: C₂₄H₁₉N₅O
• 分子量: 393.448
• InChiKey: MDDUHZUXGZTGPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  98.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-Amino-4-methylphenyl)-9-(6-aminopyridin-3-yl)benzo[h][1,6]naphthyridin-2-one 、 丙烯酰氯 在 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 生成 N-(5-(9-(6-aminopyridin-3-yl)-2-oxobenzo[h][1,6]naphthyridin-1(2H)-yl)-2-methylphenyl)acrylamide
  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
• 作为产物：
  描述：

  4,6-二氯喹啉-3-羧酸乙酯 在 manganese(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 tin(II) chloride dihdyrate 、 sodium carbonate 、 potassium carbonate 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 生成 1-(3-Amino-4-methylphenyl)-9-(6-aminopyridin-3-yl)benzo[h][1,6]naphthyridin-2-one
  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

• SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF
  申请人：Whitehead Institute for Biomedical Research

  公开号：US20130072485A1

  公开（公告）日：2013-03-21

  The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.

  本发明涉及mTORC1和mTORC2的小分子调节剂，其合成和中间体。这种小分子调节剂在治疗增殖性疾病（例如良性肿瘤、癌症、炎症性疾病、自身免疫性疾病、糖尿病视网膜病）和代谢性疾病中有用。提供了新的小分子，可抑制mTORC1、mTORC2和PI3K相关蛋白中的一个或多个。还讨论了提供可溶性mTORC1和mTORC2复合物的新方法，以及使用可溶性复合物以高通量方式筛选抑制化合物的方法。
• INHIBITORS OF MTOR KINASE AS ANTI-VIRAL AGENTS
  申请人：Moorman Nathaniel

  公开号：US20120190676A1

  公开（公告）日：2012-07-26

  The present invention provides methods and compositions for treating or preventing viral infections using modulators of host cell enzymes relating to mTOR. The invention also provides methods and compositions for treating or preventing viral infections using modulators of host cell enzymes relating to mTOR and modulators of the unfolded protein response.
• US8889706B2
  申请人：——

  公开号：US8889706B2

  公开（公告）日：2014-11-18
• [EN] SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF<br/>[FR] COMPLEXES MTOR SOLUBLES ET MODULATEURS ASSOCIÉS
  申请人：WHITEHEAD BIOMEDICAL INST

  公开号：WO2010044885A2

  公开（公告）日：2010-04-22

  The present invention relates to small molecule modulators of mTORCl and mT0RC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORCl, mT0RC2, and PI3K-related proteins. Novel methods of providing soluble mTORCl and mT0RC2 complexes are discussed, as well as methods of using the soluble complexes in a high- throughput manner to screen for inhibitory compounds.
• Structure–Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent
  作者：Yanke Liang、Melissanne de Wispelaere、Margot Carocci、Qingsong Liu、Jinhua Wang、Priscilla L. Yang、Nathanael S. Gray

  DOI：10.1021/acsmedchemlett.7b00008

  日期：2017.3.9

  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.