2-N-Acetylamino-3-methoxybenzamide | 172462-98-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-N-Acetylamino-3-methoxybenzamide
• 英文别名: 2-Acetamido-3-methoxybenzamide
• CAS: 172462-98-5
• 化学式: C₁₀H₁₂N₂O₃
• 分子量: 208.217
• InChiKey: DYORJPFKMBJLOB-UHFFFAOYSA-N

物化性质

• 沸点：
  382.6±32.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-N-Acetylamino-3-methoxybenzamide 在 sodium hydroxide 、 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 34.0h， 生成 8-羟基-2,3-二甲基-4(3H)-喹唑啉酮
  参考文献：
  名称：

  Resistance-Modifying Agents. 5. Synthesis and Biological Properties of Quinazolinone Inhibitors of the DNA Repair Enzyme Poly(ADP-ribose) Polymerase (PARP)

  摘要：

  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.

  DOI：

  10.1021/jm980273t
• 作为产物：
  描述：

  3-甲氧基-2-氨基苯甲酰胺 、 乙酰氯 生成 2-N-Acetylamino-3-methoxybenzamide
  参考文献：
  名称：

  [EN] NEUROLOGICALLY-ACTIVE COMPOUNDS
  [FR] COMPOSÉS NEUROLOGIQUEMENT ACTIFS

  摘要：

  本发明涉及具有两个融合的6元环，其中第1位置有一个氮原子，第8位置有一个羟基或巯基基团的神经活性化合物，其中至少一个环是芳香环。还公开了制备这些化合物的方法以及它们作为药物或兽药剂的用途，特别是用于治疗神经系统疾病，更具体地说是神经退行性疾病，如阿尔茨海默病。

  公开号：

  WO2004031161A1

文献信息

• [EN] NEUROLOGICALLY-ACTIVE COMPOUNDS<br/>[FR] COMPOSÉS NEUROLOGIQUEMENT ACTIFS
  申请人：PRANA BIOTECHNOLOGY LTD

  公开号：WO2004031161A1

  公开（公告）日：2004-04-15

  The present invention relates to neurologically-active compounds, being heterocyclic compounds having two fused 6-membered rings with a nitrogen atom at position 1 and a hydroxy or mercapto group at position 8 with at least one ring being aromatic. Also disclosed are processes for the preparation of these compounds and their use as pharmaceutical or veterinary agents, in particular for the treatment of neurological conditions, more specifically neurodegenerative conditions such as Alzheimer's disease.

  本发明涉及具有两个融合的6元环，其中第1位置有一个氮原子，第8位置有一个羟基或巯基基团的神经活性化合物，其中至少一个环是芳香环。还公开了制备这些化合物的方法以及它们作为药物或兽药剂的用途，特别是用于治疗神经系统疾病，更具体地说是神经退行性疾病，如阿尔茨海默病。
• Benzamide analogs useful as PARP (ADP-ribosyltransferase, ADPRT) DNA
  申请人：Newcastle University Ventures Limited

  公开号：US05756510A1

  公开（公告）日：1998-05-26

  A range of 3-oxybenzamide compounds and related quinazolinone compounds are disclosed which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. The compounds disclosed include 3-benzyloxybenzamides, 3-oxybenzamides in which a chain of 5 or more methylene groups terminate in a halogen atom or in a purin-9-yl moiety, certain benzoxazole-4-carboxamide compounds and certain quinazolinone compounds. In formula X and Y together may form a bride --X--Y-- that represents the grouping (a), (b) or (c )wherein R.sup.5 is H, alkyl, aryl or aralkyl.

  揭示了一系列3-氧苯甲酰胺化合物和相关的喹唑啉酮化合物，它们可以作为DNA修复酶聚(ADP-核糖)聚合酶或PARP酶（EC 2.4.2.30）的有效抑制剂，并且因此可以提供用于与损伤DNA的细胞毒性药物或放疗结合使用以增强后者效果的有用治疗化合物。所披露的化合物包括3-苄氧基苯甲酰胺、3-氧基苯甲酰胺，其中5个或更多亚甲基基团的链以卤原子或吡嗪-9-基团结尾，某些苯并噁唑-4-甲酰胺化合物和某些喹唑啉酮化合物。在公式X和Y中，X和Y一起可以形成代表基团(a)、(b)或(c)的桥--X--Y--，其中R.sup.5为H、烷基、芳基或芳基烷基。
• NEUROLOGICALLY ACTIVE COMPOUNDS
  申请人：Barnham Kevin Jeffrey

  公开号：US20100160346A1

  公开（公告）日：2010-06-24

  The present invention relates to neurologically-active compounds, processes for their preparation and their use as pharmaceutical or veterinary agents, in particular for the treatment of neurological conditions, more specifically neurodegenerative conditions such as Alzheimer's disease.

  本发明涉及神经活性化合物，其制备方法以及它们作为制药或兽医制剂的用途，特别是用于治疗神经系统疾病，更具体地说是神经退行性疾病，如阿尔茨海默病。
• QUINAZOLINONE CONPOUNDS AS CHEMOTHERAPEUTIC AGENTS
  申请人：NEWCASTLE UNIVERSITY VENTURES LIMITED

  公开号：EP0897915A1

  公开（公告）日：1999-02-24

  A range of quinazolinone compounds are disclosed which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. The compounds disclosed comprise certain quinazolinone compounds having the general structural formula II or pharmaceutically acceptable salt thereof, characterised in that X' represents hydroxyl, alkyl, alkoxy or an optionally substituted aryl (e.g. phenyl) or aralkyl (e.g. benzyl) group, and Y' represents hydrogen, alkyl or an optionally substituted aryl (e.g. phenyl) or aralkyl (e.g. benzyl) group.

  本发明公开了一系列喹唑啉酮化合物，它们可以作为 DNA 修复酶聚（ADP-核糖）聚合酶或 PARP 酶（EC 2.4.2.30）的强效抑制剂，从而可以提供有用的治疗化合物，与破坏 DNA 的细胞毒性药物或放射治疗一起使用，以增强后者的效果。所公开的化合物包括某些具有通式 II 结构的喹唑啉酮化合物 或其药学上可接受的盐、 其特征在于 X'代表羟基、烷基、烷氧基或任选取代的芳基（如苯基）或芳烷基（如苄基）、 和 Y' 代表氢、烷基或任选取代的芳基（如苯基）或芳烷基（如苄基）。
• 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：——