8-methoxy-2-(4-nitrophenyl)quinazolin-4-one | 181135-49-9

• 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: 8-methoxy-2-(4-nitrophenyl)quinazolin-4-one
• 英文别名: 8-Methoxy-2-(4-nitro-phenyl)-3H-quinazolin-4-one；8-methoxy-2-(4-nitrophenyl)-3H-quinazolin-4-one
• CAS: 181135-49-9
• 化学式: C₁₅H₁₁N₃O₄
• 分子量: 297.27
• InChiKey: PGAMJHQYVDYIQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  96.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-methoxy-2-(4-nitrophenyl)quinazolin-4-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以68%的产率得到2-(4-硝基苯基)-4,8-喹唑啉二醇
  参考文献：
  名称：

  2-芳基喹唑啉-4-酮作为tankyrases的高选择性和强效抑制剂的构效关系

  摘要：

  Tankyrases (TNKSs) 是 PARP（聚（ADP-核糖）聚合酶）酶超家族的成员，作为治疗药物靶点引起了人们的兴趣，特别是因为它们参与 Wnt 信号传导的调节。合成了一系列在 8 位具有不同取代基的 2-芳基喹唑啉-4-酮。8-甲基（与 8-H、8-OMe、8-OH 相比）与 4'-疏水或吸电子基团一起对 TNKS 提供了最大的效力和选择性。所选化合物与 TNKS-2 的共晶结构表明，与 PARP-1/2 相比，TNKS-2 中 8 位附近的蛋白质更具疏水性，从而使选择性合理化。NAD +-结合位点包含容纳 2-芳基的疏水腔；在 TNKS-2 中，它有一条通往外部的隧道，但在 PARP-1 中空腔是封闭的。8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one 被确定为 TNKSs 和 Wnt 信号传导的有效和选择性抑制剂。这种

  DOI：

  10.1016/j.ejmech.2016.04.041
• 作为产物：
  描述：

  2-氨基-3-甲氧基苯甲酸 在 吡啶 、 ammonium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 8-methoxy-2-(4-nitrophenyl)quinazolin-4-one
  参考文献：
  名称：

  2-芳基喹唑啉-4-酮作为tankyrases的高选择性和强效抑制剂的构效关系

  摘要：

  Tankyrases (TNKSs) 是 PARP（聚（ADP-核糖）聚合酶）酶超家族的成员，作为治疗药物靶点引起了人们的兴趣，特别是因为它们参与 Wnt 信号传导的调节。合成了一系列在 8 位具有不同取代基的 2-芳基喹唑啉-4-酮。8-甲基（与 8-H、8-OMe、8-OH 相比）与 4'-疏水或吸电子基团一起对 TNKS 提供了最大的效力和选择性。所选化合物与 TNKS-2 的共晶结构表明，与 PARP-1/2 相比，TNKS-2 中 8 位附近的蛋白质更具疏水性，从而使选择性合理化。NAD +-结合位点包含容纳 2-芳基的疏水腔；在 TNKS-2 中，它有一条通往外部的隧道，但在 PARP-1 中空腔是封闭的。8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one 被确定为 TNKSs 和 Wnt 信号传导的有效和选择性抑制剂。这种

  DOI：

  10.1016/j.ejmech.2016.04.041

文献信息

• [EN] TANKYRASE INHIBITORS<br/>[FR] INHIBITEURS DE TANKYRASE
  申请人：UNIV BATH

  公开号：WO2014087165A1

  公开（公告）日：2014-06-12

  The present invention relates to a compound of formula I wherein X is C(R6) or N, Y is C or N, and ring A, ring B, R1 and R2 have the meanings defined herein, provided that when ring B is carbocyclic, X is C(R6); or a pharmaceutically acceptable salt or solvate thereof. The compounds are tankyrase-1 and tankyrase-2 inhibitors and are useful in the treatment of a number of conditions, including cancer.

  本发明涉及一种具有式I的化合物，其中X为C(R6)或N，Y为C或N，环A、环B、R1和R2具有本文中定义的含义，前提是当环B为碳环时，X为C(R6)；或其药学上可接受的盐或溶剂。这些化合物是坦克酶-1和坦克酶-2抑制剂，并可用于治疗多种疾病，包括癌症。
• Quinazolinone compounds
  申请人：Newcastle University Ventures Limited

  公开号：US06156739A1

  公开（公告）日：2000-12-05

  Phosphate derivatives are disclosed of quinazolinone compounds having structural formula (I) or a pharmaceutically acceptable salt thereof, wherein X' represent hydroxyl, alkyl, alkoxy, or O--Z where Z is a phosphate or phosphate derivative; Y' represents hydrogen, alkyl or an optionally substituted aryl group or optionally substituted aralkyl group; and R' is hydrogen, alkyl, or CH.sub.2 --O--Z where Z is again a phosphate or phosphate derivative; subject to the proviso that if neither X' nor R' contains Z, Y' is an aryl or aralkyl group having an O--Z substituent therein with Z once again being a phosphate or phosphate derivative as hereinabove defined. These compounds are useful as prodrugs for providing active PARP inhibiting substances for medical use in conjunction with a cytotoxic drug or radiotherapy in order to increase the effectiveness of the latter, especially in connection with antitumor treatment. ##STR1##

  磷酸盐衍生物被披露为具有结构式（I）的喹唑啉酮化合物或其药用可接受的盐，其中X'代表羟基、烷基、烷氧基或O-Z，其中Z是磷酸盐或磷酸盐衍生物；Y'代表氢、烷基或可选择取代的芳基或可选择取代的芳基烷基；R'是氢、烷基或CH.sub.2-O-Z，其中Z再次是磷酸盐或磷酸盐衍生物；但是如果X'和R'都不含Z，则Y'是具有O-Z取代基的芳基或芳基烷基，其中Z再次是磷酸盐或磷酸盐衍生物，如上所定义。这些化合物可用作前药，用于提供用于与细胞毒性药物或放疗一起用于医疗用途的活性PARP抑制物质，以增强后者的效果，特别是在抗肿瘤治疗方面。
• Resistance-Modifying Agents. 5. Synthesis and Biological Properties of Quinazolinone Inhibitors of the DNA Repair Enzyme Poly(ADP-ribose) Polymerase (PARP)
  作者：Roger J. Griffin、Sheila Srinivasan、Karen Bowman、A. Hilary Calvert、Nicola J. Curtin、David R. Newell、Louise C. Pemberton、Bernard T. Golding

  DOI：10.1021/jm980273t

  日期：1998.12.1

  Clinical studies concerning the role of poly(ADP-ribose) polymerase (PARP) in the repair of drug- and radiation-induced DNA damage have been impeded by the poor solubility, lack of potency, and limited specificity of currently available inhibitors. A series of 2-alkyl- and 2-aryl-substituted 8-hydroxy-, 8-methoxy-, and 8-methylquinazolin-4(3H)-ones has been synthesized and evaluated for PARP inhibitory activity in permeabilized L1210 murine leukemia cells. 8-Methoxy- and 8-methylquinazolinones (14-34) were readily prepared by acylation of 3-substituted anthranilamides with the appropriate acid chloride, followed by base-catalyzed cyclization. The requisite 8-hydroxyquinazolinones (6, 35-39) were synthesized by demethylation of the corresponding 8-methoxyquinazolinones with BBr3. N-Methylation of 8-methoxy-2-methylquinazolinone (15) with Mel, followed by O-demethylation by BBr3, afforded the control N-3-methylquinazolinones 42 and 43, respectively. In general, an 8-hydroxy or 8-methyl substituent enhanced inhibitory activity in comparison with an 8-methoxy group. 2-Phenylquinazolinones were marginally less potent than the corresponding 2-methylquinazolinones, but the introduction of an electron-withdrawing or electron-donating 4'-substituent on the 2-aryl ring invariably increased potency. This was particularly evident in the 8-methylquinazolinone series (IC50 values 0.13-0.27 mu M), which are among the most potent PARP inhibitors reported to date. N-3-Methylquinazolinones 42 and 43 were essentially devoid of activity (IC50 values > 100 mu M). In studies with L1210 cells in vitro, a concentration of 200 mu M 8-hydroxy-2-methylquinazolinone (6, NU1025) (IC50 value 0.40 mu M) potentiated the cytotoxicity of the monomethylating agent 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide and gamma-radiation 3.5- and 1.4-fold, respectively, at the 10% survival level.
• Griffin; Srinivasan; White, Pharmaceutical Sciences, 1996, vol. 2, # 1, p. 43 - 47
  作者：Griffin、Srinivasan、White、Bowman、Calvert、Curtin、Newell、Golding

  DOI：——

  日期：——
• QUINAZOLINONE COMPOUNDS
  申请人：NEWCASTLE UNIVERSITY VENTURES LIMITED

  公开号：EP0966476A1

  公开（公告）日：1999-12-29