3-(2-chloro-phenyl)-6-fluoro-2-[2-(2-fluoro-phenyl)-2-hydroxy-vinyl]-3H-quinazolin-4-one | 291276-26-1

• 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: 3-(2-chloro-phenyl)-6-fluoro-2-[2-(2-fluoro-phenyl)-2-hydroxy-vinyl]-3H-quinazolin-4-one
• 英文别名: 3-(2-chlorophenyl)-6-fluoro-2-[(Z)-2-(2-fluorophenyl)-2-hydroxyethenyl]quinazolin-4-one
• CAS: 291276-26-1
• 化学式: C₂₂H₁₃ClF₂N₂O₂
• 分子量: 410.807
• InChiKey: WZQGHABKEFBHHX-NDENLUEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-chloro-phenyl)-6-fluoro-2-[2-(2-fluoro-phenyl)-2-hydroxy-vinyl]-3H-quinazolin-4-one 在 2,6-二甲基吡啶 、 三氟甲磺酸酐 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 四氢呋喃 为溶剂， 反应 2.5h， 以93%的产率得到3-(2-Chloro-phenyl)-6-fluoro-2-(2-fluoro-phenylethynyl)-3H-quinazolin-4-one
  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-乙酰氨基-5-氟苯甲酸 在 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 生成 3-(2-chloro-phenyl)-6-fluoro-2-[2-(2-fluoro-phenyl)-2-hydroxy-vinyl]-3H-quinazolin-4-one
  参考文献：
  名称：

  甲喹酮衍生物是有效的非竞争性AMPA受体拮抗剂。

  摘要：

  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。

  DOI：

  10.1016/s0960-894x(00)00216-x

文献信息

• 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。
• 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
  作者：Bertrand L. Chenard、Willard M. Welch、James F. Blake、Todd W. Butler、Anthony Reinhold、Frank E. Ewing、Frank S. Menniti、Martin J. Pagnozzi

  DOI：10.1021/jm000522p

  日期：2001.5.1

  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.
• 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。