N-(2-methyl-4-oxoquinazolin-3(4H)-yl)-3-[4-(4-nitrophenyl)piperazin-1-yl]propanamide | 1273022-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(2-methyl-4-oxoquinazolin-3(4H)-yl)-3-[4-(4-nitrophenyl)piperazin-1-yl]propanamide
• 英文别名: N-(2-methyl-4-oxoquinazolin-3-yl)-3-[4-(4-nitrophenyl)piperazin-1-yl]propanamide
• CAS: 1273022-43-7
• 化学式: C₂₂H₂₄N₆O₄
• 分子量: 436.47
• InChiKey: BNJVBJNDNOYAEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氨基-2-甲基-4(3H)喹唑啉酮 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 6.0h， 生成 N-(2-methyl-4-oxoquinazolin-3(4H)-yl)-3-[4-(4-nitrophenyl)piperazin-1-yl]propanamide
  参考文献：
  名称：

  Molecular modeling study and synthesis of quinazolinone-arylpiperazine derivatives as α1-adrenoreceptor antagonists

  摘要：

  Three series of new 2-[(4-substituted piperazin-1-yl) methyliquinazolin-4(3H)-ones 4a-c, Ethyl 6,7-dimethoxy-4-oxo-3-[2-(4-substituted piperazin-1-yl)acetamido/propanamido]-3,4-dihydroquinazoline-2-carboxylates 9a-f and their 2-methyl analogues 13a-I were designed and synthesized as promising alpha(1)-adrenoceptor antagonists. The final compounds were evaluated for their in vivo hypotensive activity in normotensive cats. The most potent hypotensive quinazolinone derivatives 4b, 9e, 13i, 13j were further tested on isolated thoracic aortic rings of male Wister rats. All the tested compounds displayed alpha(1)-blocking activity with IC50 ranging from 0.2 to 0.4 mM less than prazosin. Furthermore, in the present work, molecular modeling study using Accelrys Discovery Studio 2.1 software was performed by mapping the synthesized compounds to the alpha(1)-adrenoceptor antagonist hypothesis in order to predict their mechanism of action. Compound 13j which has the best-fitting score displayed the highest in vivo and in vitro activity among the tested compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.045

文献信息

• Molecular modeling study and synthesis of quinazolinone-arylpiperazine derivatives as α1-adrenoreceptor antagonists
  作者：Sahar Mahmoud Abou-Seri、Khaled Abouzid、Dalal A. Abou El Ella

  DOI：10.1016/j.ejmech.2010.11.045

  日期：2011.2

  Three series of new 2-[(4-substituted piperazin-1-yl) methyliquinazolin-4(3H)-ones 4a-c, Ethyl 6,7-dimethoxy-4-oxo-3-[2-(4-substituted piperazin-1-yl)acetamido/propanamido]-3,4-dihydroquinazoline-2-carboxylates 9a-f and their 2-methyl analogues 13a-I were designed and synthesized as promising alpha(1)-adrenoceptor antagonists. The final compounds were evaluated for their in vivo hypotensive activity in normotensive cats. The most potent hypotensive quinazolinone derivatives 4b, 9e, 13i, 13j were further tested on isolated thoracic aortic rings of male Wister rats. All the tested compounds displayed alpha(1)-blocking activity with IC50 ranging from 0.2 to 0.4 mM less than prazosin. Furthermore, in the present work, molecular modeling study using Accelrys Discovery Studio 2.1 software was performed by mapping the synthesized compounds to the alpha(1)-adrenoceptor antagonist hypothesis in order to predict their mechanism of action. Compound 13j which has the best-fitting score displayed the highest in vivo and in vitro activity among the tested compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.