[4-(2-Hydroxy-3-isopropylamino-propoxy)-phenyl]-acetic acid adamantan-1-ylmethyl ester | 101479-72-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [4-(2-Hydroxy-3-isopropylamino-propoxy)-phenyl]-acetic acid adamantan-1-ylmethyl ester
• 英文别名: 1-Adamantylmethyl 2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]acetate
• CAS: 101479-72-5
• 化学式: C₂₅H₃₇NO₄
• 分子量: 415.573
• InChiKey: YSIUGVQECHLPDW-UHFFFAOYSA-N

物化性质

• 沸点：
  551.1±45.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 4-(2-tetrahydropyranyloxy)phenylacetate 在 sodium hydroxide 、 草酸 、 sodium hydride 、 对甲苯磺酸 作用下， 以 吡啶 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 95.0h， 生成 [4-(2-Hydroxy-3-isopropylamino-propoxy)-phenyl]-acetic acid adamantan-1-ylmethyl ester
  参考文献：
  名称：

  Soft drugs. 7. Soft .beta.-blockers for systemic and ophthalmic use

  摘要：

  The "inactive metabolite approach" was used to design a series of "soft" drugs derived from the acidic metabolite of metoprolol. Pharmacokinetic and pharmacodynamic properties of these novel "soft" beta-adrenoceptor antagonists were determined: half-lives in human blood ranged from 5 to 754 min. The rates of in vivo disappearance of representative slow, medium, and fast hydrolyzing esters were determined in rats. In each case rapid and quantitative conversion to the corresponding free acid was observed. This suggests a facile, one-step degradation to the predicted major metabolite. The compounds were tested for their ability to decrease intraocular pressure in a rabbit model. Five of the new compounds exerted an ocular hypotensive action comparable to or greater than that of the reference compound, timolol maleate, and with a prolonged duration of action in some cases. In contrast the new compounds showed reduced and shorter duration systemic activity. The adamantylethyl ester emerges as a potentially effective antiglaucoma agent with significantly improved site-specific activity.

  DOI：

  10.1021/jm00403a028

文献信息

• BODOR, NICOLAS;AHMED, A. N., EGYPT. J. PHARM. SCI., 29,(1988) N 1-4, C. 179-189
  作者：BODOR, NICOLAS、AHMED, A. N.

  DOI：——

  日期：——
• Soft drugs. 7. Soft .beta.-blockers for systemic and ophthalmic use
  作者：Nicholas Bodor、Alaaeldin A. El-Koussi、Masanobu Kano、Mohamed M. Khalifa

  DOI：10.1021/jm00403a028

  日期：1988.8

  The "inactive metabolite approach" was used to design a series of "soft" drugs derived from the acidic metabolite of metoprolol. Pharmacokinetic and pharmacodynamic properties of these novel "soft" beta-adrenoceptor antagonists were determined: half-lives in human blood ranged from 5 to 754 min. The rates of in vivo disappearance of representative slow, medium, and fast hydrolyzing esters were determined in rats. In each case rapid and quantitative conversion to the corresponding free acid was observed. This suggests a facile, one-step degradation to the predicted major metabolite. The compounds were tested for their ability to decrease intraocular pressure in a rabbit model. Five of the new compounds exerted an ocular hypotensive action comparable to or greater than that of the reference compound, timolol maleate, and with a prolonged duration of action in some cases. In contrast the new compounds showed reduced and shorter duration systemic activity. The adamantylethyl ester emerges as a potentially effective antiglaucoma agent with significantly improved site-specific activity.