5-<2-<<3-(1,3-benzodioxol-5-yl)-1-methylpropyl>amino>-1-hydroxyethyl>-2-methoxybenzamide | 77618-88-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 5-<2-<<3-(1,3-benzodioxol-5-yl)-1-methylpropyl>amino>-1-hydroxyethyl>-2-methoxybenzamide
• 英文别名: 5-[2-[4-(1,3-Benzodioxol-5-yl)butan-2-ylamino]-1-hydroxyethyl]-2-methoxybenzamide
• CAS: 77618-88-3
• 化学式: C₂₁H₂₆N₂O₅
• 分子量: 386.448
• InChiKey: XYORPFAZUCCVPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 5-<2-<<3-(1,3-benzodioxol-5-yl)-1-methylpropyl>amino>-1-hydroxyethyl>-2-methoxybenzoate 在 氨 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 5-<2-<<3-(1,3-benzodioxol-5-yl)-1-methylpropyl>amino>-1-hydroxyethyl>-2-methoxybenzamide
  参考文献：
  名称：

  Salicylamide derivatives related to medroxalol with .alpha.- and .beta.-adrenergic antagonist and antihypertensive activity

  摘要：

  Analogues of medroxalol (1) were prepared in which the carboxamide function, the phenolic hydroxy group, and the aralkylamine side chain were modified. N-alkyl-substituted amide analogues of 1 showed diminishing beta-blocking activity with increasing steric bulk of the alkyl group. This allowed the conclusion that deactivation of the phenolic hydroxy group of 1 by the carbonyl group of the amide function is responsible for the beta-adrenergic antagonistic properties of 1. This conclusion was strengthened by the finding that the phenolic O-methyl analogue 5-[2-[[3-(1,3-benzodioxol-5-yl)-1-methylpropyl]amino]-1hydroxyethyl]-2-methoxybenzamide (13) was found to have enhanced beta-adrenergic blocking activity. The finding that 13 also had decreased alpha-blocking activity compared to 1 indicated that the phenolic hydroxy group of 1 enhances alpha-adrenergic antagonism. The finding that 1 and 13 showed such a large difference in relative alpha- to beta-blocking potency while exhibiting approximately equal antihypertensive activity in spontaneously hypertensive rats was surprising. In indicated that pharmacologic properties other than alpha- and beta-adrenergic blockade may contribute to the antihypertensive activity of medroxalol. One of the analogues in which the aralkylamine side chain of 1 was replaced by a fragment of a known alpha-adrenergic receptor blocker, 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]benzamide (22), showed an interesting pharmacologic profile of potential therapeutic usefulness.

  DOI：

  10.1021/jm00135a017

文献信息

• US4221808A
  申请人：——

  公开号：US4221808A

  公开（公告）日：1980-09-09