2-chloro-N-(2-(2,4-dichlorophenoxymethyl)-4-oxo-quinazolin-3(4H)-yl)acetamide | 1150095-03-6

• 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: 2-chloro-N-(2-(2,4-dichlorophenoxymethyl)-4-oxo-quinazolin-3(4H)-yl)acetamide
• 英文别名: 2-chloro-N-[2-[(2,4-dichlorophenoxy)methyl]-4-oxoquinazolin-3-yl]acetamide
• CAS: 1150095-03-6
• 化学式: C₁₇H₁₂Cl₃N₃O₃
• 分子量: 412.66
• InChiKey: JJNDXUKJCVBVHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(2-(2,4-dichlorophenoxymethyl)-4-oxo-quinazolin-3(4H)-yl)acetamide 在 potassium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 41.5h， 生成 2-[(6-(4-chlorophenyl)-5-cyano-4-(4-hydroxyphenylamino)pyrimidin-2-yl)sulfanyl]-N-[2-(2,4-dichlorophenoxymethyl)-4-oxo-4H-quinazolin-3-yl]acetamide
  参考文献：
  名称：

  New quinazolinone–pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies

  摘要：

  Two groups of hybrid compounds: the quinazolinone dihydropyrimidines and quinazolinone pyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to give intermediate 5 which was condensed with the 2-mercaptopyrimidines 4a-c affording compounds 6a-c. These latter compounds underwent hydrolysis and N-alkylation reactions to give the dihydropyrimidine derivatives 7a-c and 8a-f, respectively. The chloro derivatives 9a-c subsequently reacted with various anilines furnishing compounds 10a-i. The anti-inflammatory activity of the synthesized compounds were evaluated using the carrageenan-induced rat paw oedema model and ulcer indices for the most active compounds were calculated. Five compounds were found more active and less ulcerogenic than diclofenac particularly compound 10g (IC50 = 116.73 mu mol/kg; ulcer index = 11.38). Compound 10g was also 2-fold more selective inhibitor of COX-2 than COX-1. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.050
• 作为产物：
  描述：

  2-(2,6-二氯苯氧基)乙酰氯 在 一水合肼 、 三乙胺 作用下， 以 乙醚 、 正丁醇 、 苯 为溶剂， 反应 38.0h， 生成 2-chloro-N-(2-(2,4-dichlorophenoxymethyl)-4-oxo-quinazolin-3(4H)-yl)acetamide
  参考文献：
  名称：

  作为潜在的抗惊厥药的某些3-取代的-2-[（（2,4-二氯苯氧基）-甲基]喹唑啉-4（3H）-one衍生物的设计与合成。

  摘要：

  设计并合成了具有抗惊厥药药理学特征的2,3-二取代喹唑啉酮衍生物和[1,2,4]三嗪基[2,3-c]喹唑啉酮系列。使用皮下戊四氮（sc PTZ）和最大电击（MES）模型筛选目标化合物的抗惊厥活性。sc PTZ测试表明，活性最高的化合物是酰胺衍生物9c，其保护剂量50（PD50）为200.53 µmol / kg（苯巴比妥酮的PD50 = 62.18 µmol / kg）；但是，这种低效价却远远超过了9c的更高安全性（LD50> 3000 mg / kg）。在MES筛选中，有7种化合物的活性等于或高于苯妥英。其中一些化合物的神经毒性低于苯妥英钠。在这两个模型中，很少有化合物（例如9c和10）有效。

  DOI：

  10.1248/cpb.c12-01064

文献信息

• Synthesis and Anticonvulsant Activity of Some Quinazolin-4-(3H)-one Derivatives
  作者：Hanan Georgey、Nagwa Abdel-Gawad、Safinaz Abbas

  DOI：10.3390/molecules13102557

  日期：——

  ) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds

  已经合成了许多3-取代的-2-（取代的苯氧基甲基）喹唑啉-4（3H）-一衍生物4a，b，5a-c，6，7a-f，8a-e和9a，b。在元素分析和光谱研究（IR，1H-NMR，MS）的基础上阐明了它们的结构。对制备的化合物的抗惊厥活性的初步评估表明，化合物4b，7b-f，8a和9b表现出显着的抗惊厥活性，而化合物6、8b和8d表现出轻度至中度活性。
• New quinazolinone–pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies
  作者：Safinaz E. Abbas、Fadi M. Awadallah、Nashwa A. Ibrahin、Eman G. Said、Gihan M. Kamel

  DOI：10.1016/j.ejmech.2012.03.050

  日期：2012.7

  Two groups of hybrid compounds: the quinazolinone dihydropyrimidines and quinazolinone pyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to give intermediate 5 which was condensed with the 2-mercaptopyrimidines 4a-c affording compounds 6a-c. These latter compounds underwent hydrolysis and N-alkylation reactions to give the dihydropyrimidine derivatives 7a-c and 8a-f, respectively. The chloro derivatives 9a-c subsequently reacted with various anilines furnishing compounds 10a-i. The anti-inflammatory activity of the synthesized compounds were evaluated using the carrageenan-induced rat paw oedema model and ulcer indices for the most active compounds were calculated. Five compounds were found more active and less ulcerogenic than diclofenac particularly compound 10g (IC50 = 116.73 mu mol/kg; ulcer index = 11.38). Compound 10g was also 2-fold more selective inhibitor of COX-2 than COX-1. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Design and Synthesis of Some 3-Substituted-2-[(2,4-dichlorophenoxy)-methyl]quinazolin-4(3<i>H</i>)-one Derivatives as Potential Anticonvulsant Agents
  作者：Safinaz El-Sayed Abbas、Fadi Mohsen Awadallah、Nashwa Ahmed Ibrahim、Eman Gaber Said、Gihan Kamel

  DOI：10.1248/cpb.c12-01064

  日期：——

  Series of 2,3-disubstituted quinazolinone derivatives and a [1,2,4]triazino[2,3-c]quinazolinone featuring the pharmacophoric elements of anticonvulsant drugs were designed and synthesized. Target compounds were screened for their anticonvulsant activity using the subcutaneous pentylenetetrazole (s.c. PTZ) and maximal electroshock (MES) models. The s.c. PTZ test showed that the most active compound

  设计并合成了具有抗惊厥药药理学特征的2,3-二取代喹唑啉酮衍生物和[1,2,4]三嗪基[2,3-c]喹唑啉酮系列。使用皮下戊四氮（sc PTZ）和最大电击（MES）模型筛选目标化合物的抗惊厥活性。sc PTZ测试表明，活性最高的化合物是酰胺衍生物9c，其保护剂量50（PD50）为200.53 µmol / kg（苯巴比妥酮的PD50 = 62.18 µmol / kg）；但是，这种低效价却远远超过了9c的更高安全性（LD50> 3000 mg / kg）。在MES筛选中，有7种化合物的活性等于或高于苯妥英。其中一些化合物的神经毒性低于苯妥英钠。在这两个模型中，很少有化合物（例如9c和10）有效。