6-(4-chloro-3-fluoro-phenyl)-7-isopropyl-2-methyl-3H-quinazolin-4-one | 681292-25-1

• 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: 6-(4-chloro-3-fluoro-phenyl)-7-isopropyl-2-methyl-3H-quinazolin-4-one
• 英文别名: 6-(4-Chloro-3-fluoro-phenyl)-7-isopropyl-2-methyl-3H-quinazolin-4-one；6-(4-chloro-3-fluorophenyl)-2-methyl-7-propan-2-yl-3H-quinazolin-4-one
• CAS: 681292-25-1
• 化学式: C₁₈H₁₆ClFN₂O
• 分子量: 330.789
• InChiKey: IWRPKTFHMYNBLG-UHFFFAOYSA-N

物化性质

• 沸点：
  486.7±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-chloro-3-fluoro-phenyl)-7-isopropyl-2-methyl-3H-quinazolin-4-one 、 环丁基甲醇 在 sodium hydride 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 6(4-chloro-3-cyclobutylmethoxy-phenyl)-7-isopropyl-2-methyl-3H-quinazoline-4-one
  参考文献：
  名称：

  Identification and Biological Characterization of 6-Aryl-7-isopropylquinazolinones as Novel TRPV1 Antagonists that Are Effective in Models of Chronic Pain

  摘要：

  Vanilloid receptor I (VR1, TRPV1) is a cation-selective ion channel that is expressed on primary afferent neurons and is upregulated following inflammation and nerve damage. Blockers of this channel may have utility in the treatment of chronic nociceptive and neuropathic pain. Here, we describe the optimization from a high throughput screening hit, of a series of 6-aryl-7-isopropylquinazolinones that are TRPV1 antagonists in vitro. We also demonstrate that one compound is active in vivo against capsaicin-induced hyperalgesia and in models of neuropathic and nociceptive pain in the rat.

  DOI：

  10.1021/jm051058x
• 作为产物：
  描述：

  4-异丙基-2-硝基-苯甲酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium 10% on activated carbon 盐酸 、 氢气 、 碘 、 sodium carbonate 、 caesium carbonate 、 silver sulfate 作用下， 以 甲醇 、 DMF (N,N-dimethyl-formamide) 、 乙醇 、 水 为溶剂， 反应 53.75h， 生成 6-(4-chloro-3-fluoro-phenyl)-7-isopropyl-2-methyl-3H-quinazolin-4-one
  参考文献：
  名称：

  [EN] QUINAZOLINONE DERIVATIVES USEFUL AS ANTI-HYPERALGESIC AGENTS
  [FR] DERIVES DE QUINAZOLINONE UTILISES COMME AGENTS ANTI-HYPERALGESIQUES

  摘要：

  本发明涉及式(I)的喹唑啉酮，其中R1是卤素；a）；b）；或c）；X是N或CR8；R2是卤素；硝基；C1-C6烷基羰基；C1-C6烷基或C3-C6环烷基；R3是C1-C6烷基；C1-C6烷氧基或氨基；以及进一步的基团具有规范中定义的含义，这些化合物具有人类辣椒素拮抗活性；用于它们的生产过程，它们作为药物的用途以及包括它们的药物组成物。

  公开号：

  WO2004033435A1

文献信息

• [EN] QUINAZOLINONE DERIVATIVES USEFUL AS ANTI-HYPERALGESIC AGENTS<br/>[FR] DERIVES DE QUINAZOLINONE UTILISES COMME AGENTS ANTI-HYPERALGESIQUES
  申请人：NOVARTIS AG

  公开号：WO2004033435A1

  公开（公告）日：2004-04-22

  The present invention relates to quinazolinones of formula (I) wherein R1 is hal; a); b); or c); X is N or CR8; R2 is hal; nitro; C1-C6alkylcarbonyl; C1-C6alkyl or C3-C6cycloalkyl; R3 is C1-C6alkyl; C1-C6alkoxy or amino; and wherein the further radicals have the meanings as defined in the specification, which compounds exhibit human vanilloid antagonistic activity; to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

  本发明涉及式(I)的喹唑啉酮，其中R1是卤素；a）；b）；或c）；X是N或CR8；R2是卤素；硝基；C1-C6烷基羰基；C1-C6烷基或C3-C6环烷基；R3是C1-C6烷基；C1-C6烷氧基或氨基；以及进一步的基团具有规范中定义的含义，这些化合物具有人类辣椒素拮抗活性；用于它们的生产过程，它们作为药物的用途以及包括它们的药物组成物。
• Quinazolinone derivatives useful as anti-hyperalgesic agents
  申请人：Culshaw James Andrew

  公开号：US20060154942A1

  公开（公告）日：2006-07-13

  The present invention relates to quinazolinones of formula (I) wherein R 1 is hal; a); b); or c); X is N or CR 8 ; R 2 is hal; nitro; C 1 -C 6 alkylcarbonyl; C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl; R 3 is C 1 -C 6 alkyl; C 1 -C 6 alkoxy or amino; and wherein the further radicals have the meanings as defined in the specification, which compounds exhibit human vanilloid antagonistic activity; to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

  本发明涉及公式(I)的喹唑啉酮，其中R1是卤素；a)；b)；或c)；X是N或CR8；R2是卤素；硝基；C1-C6烷基羰基；C1-C6烷基或C3-C6环烷基；R3是C1-C6烷基；C1-C6烷氧基或氨基；其中进一步的基团在说明书中定义了它们的含义，这些化合物表现出人类vanilloid拮抗活性；本发明还涉及它们的生产过程，它们作为药物的用途以及包含它们的药物组合物。
• QUINAZOLINONE DERIVATIVES USEFUL AS ANTI-HYPERALGESIC AGENTS
  申请人：Culshaw Andrew James

  公开号：US20080293939A1

  公开（公告）日：2008-11-27

  The present invention relates to quinazolinones of formula (I) wherein R 1 is hal; a); b); or c); X is N or CR 8 ; R 2 is hal; nitro; C 1 -C 6 alkylcarbonyl; C 1 -C 6 alkyl or C 3 -C 6 cycloalkyl; R 3 is C 1 -C 6 alkyl; C 1 -C 6 alkoxy or amino; and wherein the further radicals have the meanings as defined in the specification, which compounds exhibit human vanilloid antagonistic activity; to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

  本发明涉及式（I）的喹唑啉酮，其中R1是卤素; a); b);或c); X是N或CR8; R2是卤素; 硝基; C1-C6烷基羰基; C1-C6烷基或C3-C6环烷基; R3是C1-C6烷基; C1-C6烷氧基或氨基; 其中进一步的基团在规范中定义的含义，这些化合物表现出人类vanilloid拮抗活性; 本发明还涉及它们的制备方法，它们作为药物的用途以及包含它们的制药组合物。
• Identification and Biological Characterization of 6-Aryl-7-isopropylquinazolinones as Novel TRPV1 Antagonists that Are Effective in Models of Chronic Pain
  作者：Andrew J. Culshaw、Stuart Bevan、Martin Christiansen、Prafula Copp、Andrew Davis、Clare Davis、Alex Dyson、Edward K. Dziadulewicz、Lee Edwards、Hendrikus Eggelte、Alyson Fox、Clive Gentry、Alex Groarke、Allan Hallett、Terance W. Hart、Glyn A. Hughes、Sally Knights、Peter Kotsonis、Wai Lee、Isabelle Lyothier、Andrew McBryde、Peter McIntyre、George Paloumbis、Moh Panesar、Sadhana Patel、Max-Peter Seiler、Mohammed Yaqoob、Kaspar Zimmermann

  DOI：10.1021/jm051058x

  日期：2006.1.1

  Vanilloid receptor I (VR1, TRPV1) is a cation-selective ion channel that is expressed on primary afferent neurons and is upregulated following inflammation and nerve damage. Blockers of this channel may have utility in the treatment of chronic nociceptive and neuropathic pain. Here, we describe the optimization from a high throughput screening hit, of a series of 6-aryl-7-isopropylquinazolinones that are TRPV1 antagonists in vitro. We also demonstrate that one compound is active in vivo against capsaicin-induced hyperalgesia and in models of neuropathic and nociceptive pain in the rat.