8-羟基-2,3-二甲基-4(3H)-喹唑啉酮 | 99071-94-0

• 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: 8-羟基-2,3-二甲基-4(3H)-喹唑啉酮
• 英文名称: 8-hydroxy-2,3-dimethyl-quinazolin-4(3H)-one
• 英文别名: 8-hydroxy-2,3-dimethyl-3H-quinazolin-4-one；8-Hydroxy-2,3-dimethyl-3H-chinazolin-4-on；8-Hydroxy-3-N-methyl-2-methylquinazolin-4-[3 H]-one；8-Hydroxy-2,3-dimethylquinazolin-4(3H)-one；8-hydroxy-2,3-dimethylquinazolin-4-one
• CAS: 99071-94-0
• 化学式: C₁₀H₁₀N₂O₂
• 分子量: 190.202
• InChiKey: ZXZLKEAZFBOZJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-羟基-2,3-二甲基-4(3H)-喹唑啉酮 、 苯甲醛 生成 8-hydroxy-3-methyl-2-trans(?)-styryl-3H-quinazolin-4-one
  参考文献：
  名称：

  Iyer; Dhar, Journal Of Scientific and Industrial Research, 1958, vol. 17 C, p. 193,194

  摘要：

  DOI：
• 作为产物：
  描述：

  8-甲氧基-2-甲基喹唑啉-4(3h)-酮 在 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

文献信息

• 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。
• Sinha, S. K. P.; Kumar, Prashant, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1985, vol. 24, p. 1182 - 1184
  作者：Sinha, S. K. P.、Kumar, Prashant

  DOI：——

  日期：——
• ENEIN, M. NABIL, ABOUL;BIBERS, M.;EID, ATTIAT, I.;EL-KASHIF, H.;MOUSTAFA,+, EGYPT. J. CHEM., 1984, 27, N 3, 337-346
  作者：ENEIN, M. NABIL, ABOUL、BIBERS, M.、EID, ATTIAT, I.、EL-KASHIF, H.、MOUSTAFA,+

  DOI：——

  日期：——
• SINHA S. K. P.; KUMAR PRASHANT, INDIAN J. CHEM., 24,(1985) N 11, 1182-1184
  作者：SINHA S. K. P.、 KUMAR PRASHANT

  DOI：——

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

  公开号：EP0966476A1

  公开（公告）日：1999-12-29