2-环己基-4-((1-异丙基哌啶-4-基)氨基)-6-甲氧基喹唑啉-7-醇 | 1320288-42-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2-环己基-4-((1-异丙基哌啶-4-基)氨基)-6-甲氧基喹唑啉-7-醇
• 英文名称: 2-Cyclohexyl-6-methoxy-4-[(1-propan-2-ylpiperidin-4-yl)amino]quinazolin-7-ol
• CAS: 1320288-42-3
• 化学式: C₂₃H₃₄N₄O₂
• 分子量: 398.549
• InChiKey: OZIGFERQPQPVKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  70.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N-二甲基氨乙基乙二醇 、 2-环己基-4-((1-异丙基哌啶-4-基)氨基)-6-甲氧基喹唑啉-7-醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 2-cyclohexyl-7-(2-(2-(dimethylamino)ethoxy)ethoxy)-N-(1-isopropylpiperidin-4-yl)-6-methoxyquinazolin-4-amine
  参考文献：
  名称：

  Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines

  摘要：

  Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.

  DOI：

  10.1021/jm200903z
• 作为产物：
  描述：

  2-氨基-4-(苄氧基)-5-甲氧基苯甲腈 在 1,4-环己二烯 、 palladium 10% on activated carbon 、 双氧水 、 N,N-二异丙基乙胺 、 N,N-二乙基苯胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 8.25h， 生成 2-环己基-4-((1-异丙基哌啶-4-基)氨基)-6-甲氧基喹唑啉-7-醇
  参考文献：
  名称：

  Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines

  摘要：

  Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.

  DOI：

  10.1021/jm200903z

文献信息

• [EN] QUINAZOLINE COMPOUNDS AND THEIR USE IN THERAPY<br/>[FR] COMPOSÉS DE QUINAZOLINE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：IMP INNOVATIONS LTD

  公开号：WO2013140148A1

  公开（公告）日：2013-09-26

  This invention relates to quinazoline compounds of Formula (I) which are inhibitors of the histone lysine methyltransferase (HKMTase) EZH2, and to uses of such compounds as medicaments, in particular in the treatment of a disease or disorder in which inhibition of EZH2 provides a therapeutic or prophylactic effect.

  本发明涉及式（I）的喹唑啉化合物，其为组蛋白赖氨酸甲基转移酶（HKMTase）EZH2的抑制剂，并且涉及使用这些化合物作为药物，特别是在治疗某种疾病或紊乱中，EZH2的抑制提供治疗或预防效果。
• Quinazoline Compounds And Their Use In Therapy
  申请人：Imperial Innovations Limited

  公开号：US20150057263A1

  公开（公告）日：2015-02-26

  This invention relates to quinazoline compounds of Formula (I) which are inhibitors of the histone lysine methyltransferase (HKMTase) EZH2, and to uses of such compounds as medicaments, in particular in the treatment of a disease or disorder in which inhibition of EZH2 provides a therapeutic or prophylactic effect.

  本发明涉及公式（I）的喹嗪化合物，其是组蛋白赖氨酸甲基转移酶（HKMTase）EZH2的抑制剂，并且涉及将这些化合物用作药物的用途，特别是用于治疗抑制EZH2具有治疗或预防效果的疾病或障碍。
• QUINAZOLINE COMPOUNDS AND THEIR USE IN THERAPY
  申请人：Imperial College Innovations Limited

  公开号：EP2828250B1

  公开（公告）日：2021-03-10
• US9932317B2
  申请人：——

  公开号：US9932317B2

  公开（公告）日：2018-04-03