methyl 2-hydroxy-5-<1-hydroxy-2-<4-(2-methylphenyl)-1-piperazinyl>ethyl>benzoate | 77021-00-2

• 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: methyl 2-hydroxy-5-<1-hydroxy-2-<4-(2-methylphenyl)-1-piperazinyl>ethyl>benzoate
• 英文别名: methyl 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]ethyl]benzoate；Methyl 2-hydroxy-5-[1-hydroxy-2-[4-(2-methylphenyl)piperazin-1-yl]ethyl]benzoate
• CAS: 77021-00-2
• 化学式: C₂₁H₂₆N₂O₄
• 分子量: 370.448
• InChiKey: DHZGOKYRTUXLHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-hydroxy-5-<1-hydroxy-2-<4-(2-methylphenyl)-1-piperazinyl>ethyl>benzoate 在 氨 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 2-hydroxy-5-<1-hydroxy-2-<4-(2-methylphenyl)-1-piperazinyl>ethyl>benzamide
  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
• 作为产物：
  描述：

  methyl 2-hydroxy-5-<2-<4-(2-methylphenyl)-1-piperazinyl>acetyl>benzoate dihydrochloride 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 methyl 2-hydroxy-5-<1-hydroxy-2-<4-(2-methylphenyl)-1-piperazinyl>ethyl>benzoate
  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

• 2-Hydroxy-5-(1-hydroxy-2-piperazinylethyl)-benzoic acid derivatives
  申请人：Richardson-Merrell Inc.

  公开号：US04255575A1

  公开（公告）日：1981-03-10

  Derivatives of 2-hydroxy-5-(1-hydroxy-2-piperazinylethyl)benzoic acid are prepared which are useful for their blocking action on .alpha. and .beta.-adrenergic receptors. In addition, these compounds are useful as spasmolytic and antihypertensive agents.

  制备了2-羟基-5-(1-羟基-2-哌嗪基乙基)苯甲酸的衍生物，这些衍生物对α和β肾上腺素受体的阻滞作用很有用。此外，这些化合物还可用作解痉和降压药物。
• US4255575A
  申请人：——

  公开号：US4255575A

  公开（公告）日：1981-03-10
• Salicylamide derivatives related to medroxalol with .alpha.- and .beta.-adrenergic antagonist and antihypertensive activity
  作者：J. Martin Grisar、George P. Claxton、Thomas M. Bare、Richard C. Dage、Hsien C. Cheng、James K. Woodward

  DOI：10.1021/jm00135a017

  日期：1981.3

  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.