(adamant-1-yl)methyl 4-hydroxyphenylacetate | 114653-05-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (adamant-1-yl)methyl 4-hydroxyphenylacetate
• 英文别名: 1-adamantylmethyl 2-(4-hydroxyphenyl)acetate
• CAS: 114653-05-3
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: GUWLNVJWQLUIHM-UHFFFAOYSA-N

物化性质

• 沸点：
  437.5±20.0 °C(predicted)
• 密度：
  1.197±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (adamant-1-yl)methyl 4-hydroxyphenylacetate 在 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 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
• 作为产物：
  描述：

  ethyl 4-(2-tetrahydropyranyloxy)phenylacetate 在 sodium hydroxide 、 草酸 、 对甲苯磺酸 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 35.0h， 生成 (adamant-1-yl)methyl 4-hydroxyphenylacetate
  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

• Soft .beta.-adrenergic blocking agents
  申请人：——

  公开号：US04829086A1

  公开（公告）日：1989-05-09

  New soft .beta.-adrenergic blocking agents, useful in the treatment or prevention of cardiovascular disorders and in the treatment of glaucoma, have the formula ##STR1## wherein n is an integer from 0 to 10; R is C.sub.6 -C.sub.12 cycloalkyl-C.sub.p H.sub.2p --, C.sub.6 -C.sub.18 polycycloalkyl-C.sub.p H.sub.2p --, C.sub.6 -C.sub.18 polycycloalkenyl-C.sub.p H.sub.2p -- or C.sub.6 C.sub.12 cycloalkenyl-C.sub.p H.sub.2p -- (wherein p is 0, 1, 2 or 3), or together with the adjacent ##STR2## group represents a variety of other complex ester groupings; R.sub.1 is C.sub.1 -C.sub.7 alkyl; and Ar is a divalent radical containing at least one aromatic nucleus. The corresponding pharmaceutically acceptable acid addition salts are also described.

  新型的β-肾上腺素受体阻滞剂，可用于治疗或预防心血管疾病以及治疗青光眼，其化学式为##STR1## 其中 n 为 0 到 10 的整数；R 为 C.sub.6 -C.sub.12 环烷基-C.sub.p H.sub.2p --、C.sub.6 -C.sub.18 多环烷基-C.sub.p H.sub.2p --、C.sub.6 -C.sub.18 多环烯基-C.sub.p H.sub.2p -- 或 C.sub.6 C.sub.12 环烯基-C.sub.p H.sub.2p --（其中 p 为 0、1、2 或 3），或者与相邻的##STR2## 基团一起表示各种其他复杂的酯基团；R.sub.1 为 C.sub.1 -C.sub.7 烷基；Ar 为含有至少一个芳香核的双价基团。还描述了相应的药用可接受的酸盐衍生物。
• 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 $g(b)-ADRENERGIC BLOCKING AGENTS
  申请人：BODOR, Nicholas S.

  公开号：EP0174956B1

  公开（公告）日：1990-08-16
• US4829086A
  申请人：——

  公开号：US4829086A

  公开（公告）日：1989-05-09
• US5135926A
  申请人：——

  公开号：US5135926A

  公开（公告）日：1992-08-04