3-(2-氯-苯基)-6-氟-2-甲基-3H-喹唑啉-4-酮 | 49579-12-6

• 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: 3-(2-氯-苯基)-6-氟-2-甲基-3H-喹唑啉-4-酮
• 英文名称: 3-(2-chloro-phenyl)-6-fluoro-2-methyl-3H-quinazolin-4-one
• 英文别名: 3-(2-chlorophenyl)-6-fluoro-2-methyl-4(3H)-quinazolinone；3-(2-chloro-phenyl)-6-fluoro-2-methyl-3,4-dihydro-quinazolin-4-one；3-(2-chlorophenyl)-6-fluoro-2-methylquinazolin-4-one
• CAS: 49579-12-6
• 化学式: C₁₅H₁₀ClFN₂O
• 分子量: 288.709
• InChiKey: TYDLGASFRRAUKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  32.7
• 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：

  3-(2-氯-苯基)-6-氟-2-甲基-3H-喹唑啉-4-酮 在 sodium periodate 、 magnesium sulfate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 3-(2-氯苯基)-6-氟-2-[[(2-氟苯基)氨基]甲基]-4(3H)-喹唑啉酮
  参考文献：
  名称：

  Quinazolin-4-one α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Antagonists:  Structure−Activity Relationship of the C-2 Side Chain Tether

  摘要：

  A series of 6-fluoro-3-(2 -chlorophenyl)quinazolin-4-ones has been prepared, which contains a 2-fluorophenyl ring attached to C-2 by a variety of two-atom tethers. These compounds were used to probe the structure-activity relationship (SAR) for AMPA receptor inhibition. The relative potencies of the new compounds ranged from 11 nM. to greater than 10 muM. The differential activity of the compounds was rationalized on the basis of alterations of the 2-fluorophenyl positioning (planar and radial) relative to the quinazolin-4-one ring based on computational methods. From this effort, new AMPA receptor antagonists, containing the methylamino tether group, have been identified.

  DOI：

  10.1021/jm000522p
• 作为产物：
  描述：

  2-氨基-5-氟苯甲酸 在 溶剂黄146 作用下， 生成 3-(2-氯-苯基)-6-氟-2-甲基-3H-喹唑啉-4-酮
  参考文献：
  名称：

  阻转异构的喹唑啉-4-酮衍生物是有效的非竞争性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂。

  摘要：

  Piriqualone（1）被发现是AMPA受体的拮抗剂。对三个环中的每一个进行结构活性优化，以提供一系列有效和选择性的拮抗剂。N-3芳基周围的空间拥挤环境为要分离的阻转异构体提供了足够的热稳定性。这些阻转异构体的分离导致鉴定出（+）-38（CP-465,022），该化合物以高亲和力（IC50 = 36 nM）与AMPA受体结合并显示出有效的抗惊厥活性。

  DOI：

  10.1016/s0960-894x(00)00622-3

文献信息

• Quinazolin-4-one AMPA antagonists
  申请人：Pfizer INC

  公开号：US06627755B1

  公开（公告）日：2003-09-30

  The present invention relates to novel quinazolin-4-one derivatives of the formula wherein A is a benzo or thieno fused aromatic ring; B is phenyl, pyridyl or pyrimidyl; X is N or CH; and Y-Z is —CH2NH— or —NHCH2—; and to pharmaceutical compositions containing such compounds, and the use of such compounds to treat neurodegenerative, psychotropic, and drug and alcohol induced central and peripheral nervous system disorders.

  本发明涉及一种新型喹唑啉-4-酮衍生物，其化学式为其中A是苯并或噻吩融合芳香环；B是苯基、吡啶基或嘧啶基；X是N或CH；Y-Z是—CH2NH—或—NHCH2—；以及含有此类化合物的药物组合物，以及利用这些化合物来治疗神经退行性、精神药物、以及药物和酒精诱发的中枢和外周神经系统疾病。
• Atropisomers of 3-aryl-4(3H)-quinazolinones and their use as AMPA-receptor antagonists
  申请人：Pfizer Inc.

  公开号：US06306864B1

  公开（公告）日：2001-10-23

  The present invention relates to novel atropisomers of 2-(aryl or heteroaryl)-3-aryl-4(3H)-quinazolinones of the formula I, and their pharmaceutically acceptable salts, and pharmaceutical compositions and methods of treating neurodegenerative and CNS-trauma related conditions.

  本发明涉及公式I的新型2-(芳基或杂环芳基)-3-芳基-4(3H)-喹唑啉酮的异构体及其药用盐、药物组合物和治疗神经退行性和中枢神经系统创伤相关疾病的方法。
• Quinazoline-4-one AMPA antagonists
  申请人：Pfizer Inc

  公开号：US06060479A1

  公开（公告）日：2000-05-09

  The present invention relates to novel quinazolin-4-one derivatives of the formula I, as defined in the specification, pharmaceutical compositions containing such compounds the use of such compounds to treat neurodegenerative, psychotropic, and drug and alcohol induced central and peripheral nervous system disorders.

  本发明涉及公式I所定义的新型喹唑啉-4-酮衍生物，包含这些化合物的药物组合物，以及利用这些化合物治疗神经退行性、精神药物、以及药物和酒精诱导的中枢和外周神经系统疾病。
• Methaqualone derivatives are potent noncompetitive AMPA receptor antagonists
  作者：B.L Chenard、F.S Menniti、M.J Pagnozzi、K.D Shenk、F.E Ewing、W.M Welch

  DOI：10.1016/s0960-894x(00)00216-x

  日期：2000.6

  Quinazolin-4-one derivatives of methaqualone substituted at C-2 define a new class of noncompetitive antagonists at AMPA receptors.

  在C-2处取代的甲喹酮的喹唑啉-4-酮衍生物定义了AMPA受体上的一类新的非竞争性拮抗剂。
• Methods of preparing substituted 3-phenyl- and 3-pyridyl-4(3H)-quinazolinones and atropisomers thereof
  申请人：Pfizer Products Inc.

  公开号：EP0934934A3

  公开（公告）日：1999-10-13

  This invention is directed to methods for the preparation of quinazolin-4-one derivatives of the formula and the pharmaceutically acceptable salts and atropisomers of the formula and the pharmaceutically acceptable salts thereof, wherein Ar, R1, R2, X and Y are as defined in the specification. The quinazolin-4-one derivatives prepared according to the methods of this invention are α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) inhibitors and are useful for the treatment of various neurologic disorders and conditions including Parkinson's Disease, epilepsy, emesis, eschemia, stroke, traumatic brain and spinal cord injury, and so forth.The present invention also relates to compounds of the formulae

  本发明涉及制备公式所示的喹唑啉-4-酮衍生物及其药学上可接受的盐和异构体的方法，以及制备公式中所定义的Ar、R1、R2、X和Y的药学上可接受的盐。根据本发明方法制备的喹唑啉-4-酮衍生物是α-氨基-3-羟基-5-甲基-4-异噁唑丙酸（AMPA）抑制剂，可用于治疗各种神经疾病和病况，包括帕金森病、癫痫、呕吐、缺血、中风、创伤性脑和脊髓损伤等。本发明还涉及公式化合物。