methyl 5-<2-<4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidyl>acetyl>-2-hydroxybenzoate hydrochloride | 76310-68-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-<2-<4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidyl>acetyl>-2-hydroxybenzoate hydrochloride
• CAS: 76310-68-4
• 化学式: C₂₂H₂₃N₃O₅*ClH
• 分子量: 445.903
• InChiKey: VZGGQVKDWGCLAJ-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  methyl 5-<2-<4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidyl>acetyl>-2-hydroxybenzoate hydrochloride 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以11.3 g的产率得到methyl 5-<2-<4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl>-1-hydroxyethyl>-2-hydroxybenzoate
  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