4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-3-methylpiperazine-1-carboxylic acid ethyl ester hydrochloride | 749820-37-9

• 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: 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-3-methylpiperazine-1-carboxylic acid ethyl ester hydrochloride
• 英文别名: Ethyl 4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-3-methylpiperazine-1-carboxylate
• CAS: 749820-37-9
• 化学式: C₁₈H₂₅N₅O₄
• 分子量: 375.428
• InChiKey: ZKAZNYVSMNFRQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-3-methylpiperazine-1-carboxylic acid ethyl ester hydrochloride 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 112.0h， 以25%的产率得到6,7-dimethoxy-2-(2-methylpiperazin-1-yl)quinazolin-4-ylamine
  参考文献：
  名称：

  Structure-activity relationships in prazosin-related compounds. 2. Role of the piperazine ring on .alpha.-blocking activity

  摘要：

  Several prazosin-related compounds have been synthesized and evaluated for their blocking activity toward a-adrenoreceptors. The structural modification performed on the prazosin structure included the replacement of the piperazine ring with 2,3-dialkylpiperazine or 1,2-cyclohexanediamine moieties to characterize a lipophilic binding pocket in the alpha1-adrenoreceptor surface. Cyclohexanediamine derivatives 3-6 were almost devoid of potency and selectivity, whereas dialkylpiperazine compounds 7-14 showed high affinity and selectivity toward alpha1-adrenoreceptors. The cis derivative 13 (cyclazosin) was the most potent and selective with an alpha1/alpha2 selectivity ratio value of 7800. The particular trend of antagonist activity within cis/trans stereoisomeric compounds not only supports the presence of a lipophilic binding area on alpha1-adrenoreceptor surface but also suggests that the lipophilic pocket is endowed with a well-defined size and spatial orientation. The most active compound of the series, 13, was tested also in vivo for antihypertensive activity on spontaneously hypertensive rats. It showed an interesting long-lasting hypotensive effect, very similar to that of doxazosin, which was statistically significant 12 h after oral administration.

  DOI：

  10.1021/jm00058a005
• 作为产物：
  描述：

  2-乙氧基-1-(1-哌嗪基)乙酮 、 2-氯-4-氨基-6,7-二甲氧基喹唑啉 以 异戊醇 为溶剂， 反应 72.0h， 以42%的产率得到4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-3-methylpiperazine-1-carboxylic acid ethyl ester hydrochloride
  参考文献：
  名称：

  Structure-activity relationships in prazosin-related compounds. 2. Role of the piperazine ring on .alpha.-blocking activity

  摘要：

  Several prazosin-related compounds have been synthesized and evaluated for their blocking activity toward a-adrenoreceptors. The structural modification performed on the prazosin structure included the replacement of the piperazine ring with 2,3-dialkylpiperazine or 1,2-cyclohexanediamine moieties to characterize a lipophilic binding pocket in the alpha1-adrenoreceptor surface. Cyclohexanediamine derivatives 3-6 were almost devoid of potency and selectivity, whereas dialkylpiperazine compounds 7-14 showed high affinity and selectivity toward alpha1-adrenoreceptors. The cis derivative 13 (cyclazosin) was the most potent and selective with an alpha1/alpha2 selectivity ratio value of 7800. The particular trend of antagonist activity within cis/trans stereoisomeric compounds not only supports the presence of a lipophilic binding area on alpha1-adrenoreceptor surface but also suggests that the lipophilic pocket is endowed with a well-defined size and spatial orientation. The most active compound of the series, 13, was tested also in vivo for antihypertensive activity on spontaneously hypertensive rats. It showed an interesting long-lasting hypotensive effect, very similar to that of doxazosin, which was statistically significant 12 h after oral administration.

  DOI：

  10.1021/jm00058a005

文献信息

• Structure-activity relationships in prazosin-related compounds. 2. Role of the piperazine ring on .alpha.-blocking activity
  作者：Dario Giardina、Ugo Gulini、Maurizio Massi、Maria G. Piloni、Pierluigi Pompei、Giovanni Rafaiani、Carlo Melchiorre

  DOI：10.1021/jm00058a005

  日期：1993.3

  Several prazosin-related compounds have been synthesized and evaluated for their blocking activity toward a-adrenoreceptors. The structural modification performed on the prazosin structure included the replacement of the piperazine ring with 2,3-dialkylpiperazine or 1,2-cyclohexanediamine moieties to characterize a lipophilic binding pocket in the alpha1-adrenoreceptor surface. Cyclohexanediamine derivatives 3-6 were almost devoid of potency and selectivity, whereas dialkylpiperazine compounds 7-14 showed high affinity and selectivity toward alpha1-adrenoreceptors. The cis derivative 13 (cyclazosin) was the most potent and selective with an alpha1/alpha2 selectivity ratio value of 7800. The particular trend of antagonist activity within cis/trans stereoisomeric compounds not only supports the presence of a lipophilic binding area on alpha1-adrenoreceptor surface but also suggests that the lipophilic pocket is endowed with a well-defined size and spatial orientation. The most active compound of the series, 13, was tested also in vivo for antihypertensive activity on spontaneously hypertensive rats. It showed an interesting long-lasting hypotensive effect, very similar to that of doxazosin, which was statistically significant 12 h after oral administration.