N-{6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)methylamino]hexyl}-4-formyl-N-methylbenzamide | 328078-53-1

• 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: N-{6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)methylamino]hexyl}-4-formyl-N-methylbenzamide
• 英文别名: N-[6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]hexyl]-4-formyl-N-methylbenzamide
• CAS: 328078-53-1
• 化学式: C₂₆H₃₃N₅O₄
• 分子量: 479.579
• InChiKey: ZJBIWPJUBCEABD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-{6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)methylamino]hexyl}-4-formyl-N-methylbenzamide 在 sodium tetrahydroborate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 8.0h， 生成 N-[6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]hexyl]-4-[[6-[2-[2-[6-[[4-[6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]hexyl-methylcarbamoyl]phenyl]methylamino]hexylamino]ethyldisulfanyl]ethylamino]hexylamino]methyl]-N-methylbenzamide
  参考文献：
  名称：

  Analogues of Prazosin That Bear a Benextramine-Related Polyamine Backbone Exhibit Different Antagonism toward α₁-Adrenoreceptor Subtypes

  摘要：

  Hybrid tetraaamine disulfides 4-9 were synthesized by combining the structural features of prazosin (1), a competitive alpha (1)-adrenoreceptor antagonist, and benextramine (2), an irreversible alpha (1)/alpha (2)-adrenoreceptor antagonist, and their biological profiles at alpha (1)-adrenoreceptor subtypes were assessed by functional experiments in isolated rat vas deferens (alpha (1A)), spleen (alpha (1B)), and aorta (alpha (1D)). To verify the role of the disulfide moiety on the interaction with alpha (1)-adrenorcceptor subtypes, carbon analogues 10-15 were included in this study. All quinazolines lacking the disulfide bridge behaved, like 1, as competitive antagonists, whereas all polyamine disulfides displayed a nonhomogeneous mechanism of inhibition at the three subtypes since they were, like 2, noncompetitive antagonists at the alpha (1A) and alpha (1B) subtypes while being, unlike 2, competitive antagonists at the alpha (1D). In particular, the blocking effects were characterized by a decrease of the maximal response to noradrenaline that was affected only slightly by washings. Probably the alpha (1A) and alpha (1B) subtypes bear in the binding pocket a suitable thiol function that would suffer an interchange reaction with the disulfide moiety of the antagonist and which is missing, or not accessible, in the alpha (1D) subtype. Polyamines 8, 9, and 14, among others, emerged as promising tools for the characterization of al-adrenoreceptors, owing to their receptor subtype selectivity. Finally, the effect of nonbasic substituents on the phenyl ring of prazosin analogues 16-28 on potency and selectivity for the different subtypes can hardly be rationalized.

  DOI：

  10.1021/jm000995w
• 作为产物：
  描述：

  对醛基苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 25.0h， 生成 N-{6-[(4-amino-6,7-dimethoxyquinazolin-2-yl)methylamino]hexyl}-4-formyl-N-methylbenzamide
  参考文献：
  名称：

  Analogues of Prazosin That Bear a Benextramine-Related Polyamine Backbone Exhibit Different Antagonism toward α₁-Adrenoreceptor Subtypes

  摘要：

  Hybrid tetraaamine disulfides 4-9 were synthesized by combining the structural features of prazosin (1), a competitive alpha (1)-adrenoreceptor antagonist, and benextramine (2), an irreversible alpha (1)/alpha (2)-adrenoreceptor antagonist, and their biological profiles at alpha (1)-adrenoreceptor subtypes were assessed by functional experiments in isolated rat vas deferens (alpha (1A)), spleen (alpha (1B)), and aorta (alpha (1D)). To verify the role of the disulfide moiety on the interaction with alpha (1)-adrenorcceptor subtypes, carbon analogues 10-15 were included in this study. All quinazolines lacking the disulfide bridge behaved, like 1, as competitive antagonists, whereas all polyamine disulfides displayed a nonhomogeneous mechanism of inhibition at the three subtypes since they were, like 2, noncompetitive antagonists at the alpha (1A) and alpha (1B) subtypes while being, unlike 2, competitive antagonists at the alpha (1D). In particular, the blocking effects were characterized by a decrease of the maximal response to noradrenaline that was affected only slightly by washings. Probably the alpha (1A) and alpha (1B) subtypes bear in the binding pocket a suitable thiol function that would suffer an interchange reaction with the disulfide moiety of the antagonist and which is missing, or not accessible, in the alpha (1D) subtype. Polyamines 8, 9, and 14, among others, emerged as promising tools for the characterization of al-adrenoreceptors, owing to their receptor subtype selectivity. Finally, the effect of nonbasic substituents on the phenyl ring of prazosin analogues 16-28 on potency and selectivity for the different subtypes can hardly be rationalized.

  DOI：

  10.1021/jm000995w

文献信息

• Analogues of Prazosin That Bear a Benextramine-Related Polyamine Backbone Exhibit Different Antagonism toward α₁-Adrenoreceptor Subtypes
  作者：Maria L. Bolognesi、Gabriella Marucci、Piero Angeli、Michela Buccioni、Anna Minarini、Michela Rosini、Vincenzo Tumiatti、Carlo Melchiorre

  DOI：10.1021/jm000995w

  日期：2001.2.1

  Hybrid tetraaamine disulfides 4-9 were synthesized by combining the structural features of prazosin (1), a competitive alpha (1)-adrenoreceptor antagonist, and benextramine (2), an irreversible alpha (1)/alpha (2)-adrenoreceptor antagonist, and their biological profiles at alpha (1)-adrenoreceptor subtypes were assessed by functional experiments in isolated rat vas deferens (alpha (1A)), spleen (alpha (1B)), and aorta (alpha (1D)). To verify the role of the disulfide moiety on the interaction with alpha (1)-adrenorcceptor subtypes, carbon analogues 10-15 were included in this study. All quinazolines lacking the disulfide bridge behaved, like 1, as competitive antagonists, whereas all polyamine disulfides displayed a nonhomogeneous mechanism of inhibition at the three subtypes since they were, like 2, noncompetitive antagonists at the alpha (1A) and alpha (1B) subtypes while being, unlike 2, competitive antagonists at the alpha (1D). In particular, the blocking effects were characterized by a decrease of the maximal response to noradrenaline that was affected only slightly by washings. Probably the alpha (1A) and alpha (1B) subtypes bear in the binding pocket a suitable thiol function that would suffer an interchange reaction with the disulfide moiety of the antagonist and which is missing, or not accessible, in the alpha (1D) subtype. Polyamines 8, 9, and 14, among others, emerged as promising tools for the characterization of al-adrenoreceptors, owing to their receptor subtype selectivity. Finally, the effect of nonbasic substituents on the phenyl ring of prazosin analogues 16-28 on potency and selectivity for the different subtypes can hardly be rationalized.