8-甲氧基-2,3-二甲基-4(3H)-喹唑啉酮 | 104296-30-2

• 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-甲氧基-2,3-二甲基-4(3H)-喹唑啉酮
• 英文名称: 2,3-dimethyl-8-methoxyquinazolin-4-one
• 英文别名: 8-methoxy-2,3-dimethyl-3H-quinazolin-4-one；8-Methoxy-2,3-dimethyl-3H-chinazolin-4-on；8-methoxy-3-N-methyl-2-methylquinazolin-4-[3 H]-one；8-Methoxy-2,3-dimethylquinazolin-4(3H)-one；8-methoxy-2,3-dimethylquinazolin-4-one
• CAS: 104296-30-2
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: BUKGEOTYMNTZKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  8-甲氧基-2,3-二甲基-4(3H)-喹唑啉酮 在 氢溴酸 作用下， 生成 8-hydroxy-2-(4-methoxy-trans(?)-styryl)-3-methyl-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：

  2-N-Acetylamino-3-methoxybenzamide 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 34.0h， 生成 8-甲氧基-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

• PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS
  申请人：Gilead Sciences, Inc.

  公开号：US20140371246A1

  公开（公告）日：2014-12-18

  The present disclosure provides phosphatidylinositol 3-kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts or isomers thereof, in which n, m, R 1 , R 2 , R 4 , and R 3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts or isomers thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.

  本公开提供了式（I）的磷脂酰肌醇3-激酶（PI3K）抑制剂，或其药用盐或异构体，其中n、m、R1、R2、R4和R3如本文所定义。这些化合物可用于治疗由一个或多个PI3K同工酶介导的疾病，如PI3Kδ。本公开还提供了包括式（I）的化合物、药用盐或异构体的药物组合物，以及使用这些化合物和组合物治疗由一个或多个PI3K同工酶介导的疾病，如PI3Kδ的方法。
• N3-Alkylation during formation of quinazolin-4-ones from condensation of anthranilamides and orthoamides
  作者：Amit Nathubhai、Richard Patterson、Timothy J. Woodman、Harriet E. C. Sharp、Miranda T. Y. Chui、Hugo H. K. Chung、Stephanie W. S. Lau、Jun Zheng、Matthew D. Lloyd、Andrew S. Thompson、Michael D. Threadgill

  DOI：10.1039/c1ob05430a

  日期：——

  diverts the alkylation to the oxygen, giving 4-isopropoxyquinazolines, along with N3-methylquinazolin-4-ones where the methyl is derived from N-Me of the orthoamides. Reaction of anthranilamide with the highly sterically demanding dimethylformamide di(t-butyl)acetal gives largely quinazolin-4-one, whereas dimethylformamide di(neopentyl)acetal forms a mixture of quinazolin-4-one and N3-methylquinazolin-4-one

  二甲基甲酰胺二甲基缩醛 （DMFDMA）被广泛用作甲酸盐氧化水平的亲电一碳单元的来源; 然而，该试剂的亲电子甲基化以前尚未报道。的反应蒽酰胺 和 DMFDMA 在150°C下短时间产生 喹唑啉-4-一。然而，与二甲基甲酰胺二（伯烷基）缩醛的长时间反应导致随后在N 3处的烷基化。用3-取代的邻氨基苯甲酰胺得到8-取代的3-烷基喹唑啉-4-酮。邻氨基苯甲酰胺与二甲基乙酰胺二甲基缩醛提供2，3-二甲基喹唑啉-4-酮。在这些反应中，N 3-烷基的来源是原酰胺的O-烷基。相比之下，与空间上更拥挤的二甲基甲酰胺二（异丙基）缩醛的反应将烷基化转移至氧，得到4-异丙氧基喹唑啉，以及N 3-甲基喹唑啉-4-酮，其中甲基衍生自邻酰胺的N -Me。的反应蒽酰胺在空间上要求很高的二甲基甲酰胺二（叔丁基）缩醛喹唑啉-4-一，而二甲基甲酰胺二（新戊基）缩醛形成 喹唑啉-4-一 和 N 3-甲基喹唑啉-4-一。通过从邻
• 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。
• [EN] PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHATIDYLINOSITOL 3-KINASE
  申请人：GILEAD SCIENCES INC

  公开号：WO2014201409A1

  公开（公告）日：2014-12-18

  The present disclosure provides phosphatidylinositol 3 -kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts or isomers thereof, in which n, m, R1, R2, R4, and R3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts or isomers thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.

  本公开提供式(I)的磷脂酰肌醇3-激酶（PI3K）抑制剂，或其药学上可接受的盐或异构体，其中n，m，R1，R2，R4和R3如本文所定义。这些化合物可用于治疗由一个或多个PI3K亚型介导的疾病，例如PI3Kδ。本公开还提供包括式(I)的化合物或其药学上可接受的盐或异构体的制药组合物，以及使用这些化合物和组合物治疗由一个或多个PI3K亚型介导的疾病，例如PI3Kδ的方法。
• 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：——