2-肼基-3-(3-甲氧基苯基)喹唑啉-4-酮 | 66679-67-2

• 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: 2-肼基-3-(3-甲氧基苯基)喹唑啉-4-酮
• 英文名称: 2-hydroazino-3-(3-methoxyphenyl)-3H-quinazolin-4-one
• 英文别名: 2-hydrazino-3-(3-methoxyphenyl)-3H-quinazolin-4-one；Agn-PC-0N5swj；2-hydrazinyl-3-(3-methoxyphenyl)quinazolin-4-one
• CAS: 66679-67-2
• 化学式: C₁₅H₁₄N₄O₂
• 分子量: 282.302
• InChiKey: WRTYMUJLXASZCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  80
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-肼基-3-(3-甲氧基苯基)喹唑啉-4-酮 、 丁二酸二乙酯 反应 5.0h， 以26%的产率得到3-[4-(3-Methoxy-phenyl)-5-oxo-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinazolin-1-yl]-propionic acid ethyl ester
  参考文献：
  名称：

  Kottke; Kuhmstedt; Knoke, Pharmazie, 1983, vol. 38, # 1, p. 25 - 28

  摘要：

  DOI：
• 作为产物：
  描述：

  3-(3-methoxyphenyl)-2-methylsulfanyl-3H-quinazolin-4-one 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 35.0h， 以79%的产率得到2-肼基-3-(3-甲氧基苯基)喹唑啉-4-酮
  参考文献：
  名称：

  4-(3-Methoxyphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5- ones: new class of H1-antihistaminic agents

  摘要：

  通过 2-肼基-3-(3-甲氧基苯基)-3H-喹唑啉-4-酮与各种亲电子体的环化反应，合成了一系列 1-取代-4-(3-甲氧基苯基)-4H-[1,2,4]三唑并[4,3-a]喹唑啉-5-酮。起始原料 2-肼基-3-(3-甲氧基苯基)-3H-喹唑啉-4-酮是通过创新路线从 2-甲氧基苯胺合成的。对标题化合物在豚鼠体内的 H1 抗组胺活性进行了测试；所有测试化合物都能显著保护动物免受组胺引起的支气管痉挛。化合物 1-甲基-4-(3-甲氧基苯基)-4H-[1,2,4]三唑并[4,3-a]喹唑啉-5-酮（II）是该系列中活性最强的化合物，其药效（72.76%）高于参考标准马来酸氯苯那敏（71%）。与马来酸氯苯那敏（25%）相比，化合物 II 的镇静作用（10%）可忽略不计。因此，它可以作为一种新的 H1 类抗组胺药的原型分子进行进一步开发。

  DOI：

  10.1691/ph.2008.8670

文献信息

• 4-(3-Methoxyphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5- ones: new class of H1-antihistaminic agents
  作者：Alagarsamy, Veerachamy、Sharma、Parthiban、Hanish Singh、Thirusenthil Murugan、Raja Solomon

  DOI：10.1691/ph.2008.8670

  日期：——

  A series of 1-substituted-4-(3-methoxyphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-(3-methoxyphenyl)-3H-quinazolin-4-one with various electrophile. The starting material 2-hydrazino-3-(3-methoxyphenyl)-3H-quinazolin-4-one was synthesized from 2-methoxy aniline by an innovative route. Title compounds were tested for their in vivo H1-antihistaminic activity on guinea pigs; all the tested compounds protected the animals from histamine induced bronchospasm significantly. Compound 1-methyl-4-(3-methoxyphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (II) emerged as the most active compound of the series and was more potent (72.76%) than the reference standard chlorpheniramine maleate (71%). Compound II showed negligible sedation (10%) when compared to chlorpheniramine maleate (25%). Hence it could serve as prototype molecule for further development as a new class of H1-antihistaminic agents.

  通过 2-肼基-3-(3-甲氧基苯基)-3H-喹唑啉-4-酮与各种亲电子体的环化反应，合成了一系列 1-取代-4-(3-甲氧基苯基)-4H-[1,2,4]三唑并[4,3-a]喹唑啉-5-酮。起始原料 2-肼基-3-(3-甲氧基苯基)-3H-喹唑啉-4-酮是通过创新路线从 2-甲氧基苯胺合成的。对标题化合物在豚鼠体内的 H1 抗组胺活性进行了测试；所有测试化合物都能显著保护动物免受组胺引起的支气管痉挛。化合物 1-甲基-4-(3-甲氧基苯基)-4H-[1,2,4]三唑并[4,3-a]喹唑啉-5-酮（II）是该系列中活性最强的化合物，其药效（72.76%）高于参考标准马来酸氯苯那敏（71%）。与马来酸氯苯那敏（25%）相比，化合物 II 的镇静作用（10%）可忽略不计。因此，它可以作为一种新的 H1 类抗组胺药的原型分子进行进一步开发。
• Novel Nonpeptide CCK-B Antagonists:  Design and Development of Quinazolinone Derivatives as Potent, Selective, and Orally Active CCK-B Antagonists
  作者：Janak K. Padia、Mark Field、Joanna Hinton、Ken Meecham、Julius Pablo、Rob Pinnock、Bruce D. Roth、Lakhbir Singh、Nirmala Suman-Chauhan、Bharat K. Trivedi、Louise Webdale

  DOI：10.1021/jm970373j

  日期：1998.3.1

  We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our "target" produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.
• KOTTKE K.; KUEHMSTEDT H., PHARMAZIE, 1978, 33, NO 1, 19-23
  作者：KOTTKE K.、 KUEHMSTEDT H.

  DOI：——

  日期：——
• KOTTKE K.; KOHMSTEDT H., PHARMAZIE, 1978, 33, NO 2-3, 125-126
  作者：KOTTKE K.、 KOHMSTEDT H.

  DOI：——

  日期：——
• KOTTKE K.; KUHMSTEDT H., PHARMAZIE, 1978, 33, NO 2-3, 124-125
  作者：KOTTKE K.、 KUHMSTEDT H.

  DOI：——

  日期：——