外消旋7-甲氧基普萘洛尔 | 76275-53-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 外消旋7-甲氧基普萘洛尔
• 英文名称: 1-Isopropylamino-3-(7-methoxy-naphthalen-1-yloxy)-propan-2-ol
• 英文别名: rac 7-Methoxy Propranolol；1-(7-methoxynaphthalen-1-yl)oxy-3-(propan-2-ylamino)propan-2-ol
• CAS: 76275-53-1
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: SHLYYDPCAGPWOZ-UHFFFAOYSA-N

物化性质

• 熔点：
  74-76°C
• 沸点：
  467.6±35.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  50.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  外消旋7-甲氧基普萘洛尔 在 吡啶盐酸盐 作用下， 反应 15.0h， 生成 7-羟基普萘洛尔
  参考文献：
  名称：

  Ring-hydroxylated propranolol: synthesis and .beta.-receptor antagonist and vasodilating activities of the seven isomers

  摘要：

  Propranolol (Inderal; 1) is extensively metabolized in man. Metabolites of interest pharmacologically include ring-hydroxylated propranolols (1a-g). In order to identify these ring-oxidized products and to study the effect of hydroxyl position on biological activity, we have synthesized all seven isomers. With the exception of 1b and 1g, the desired compounds were prepared by alkylation of the respective methoxy-1-naphthols with epichlorohydrin and reaction of the resulting epoxide with isopropylamine. Cleavage og the methyl group in fused pyridine hydrochloride afforded 1a,c-f. 1g was prepared by the direct alkylation of 1,8-naphthalenediol (17) with epichlorohydrin, followed by reaction with isopropylamine. 1b was synthesized by treating 2-naphthol (9) with chlorine gas and then treating the resulting 1,1-dichloronaphthalen-2(1H)-one (10) with sodium allyl oxide. Acetylation of the hydroxy function and epoxidatrion of the allyl group, followed by relation with isopropylamine, gave 3'-hydroxy-4'-chloropropranolol (15). Dechlorination gave 1b. All of the racemic hydroxylated propranolols produced beta blockade and direct vasodilation in anesthetized dogs. The potency is strongly dependent upon the position of the hydroxyl group, i.e., 1e is 4 times as potent as 1 as a beta receptor antagonist, whereas 1a, 1b, and 1g are all significantly less potent than 1. For direct vasodilation, 1a and 1g are equipotent to 1, while 1b-f are much less potent. The potencies of the compounds were also compared with their 1-octanol/pH 7.4 buffer distribution coefficients; the direct vasodilating potency was found to increase with increasing lipophilicity, while the beta-adrenergic antagonist potency decreased.

  DOI：

  10.1021/jm00135a014
• 作为产物：
  描述：

  7-甲氧基萘-1-醇 、 异丙胺 、 环氧氯丙烷 在 Dowex-1 resin (OH form) 作用下， 生成 外消旋7-甲氧基普萘洛尔
  参考文献：
  名称：

  Ring-hydroxylated propranolol: synthesis and .beta.-receptor antagonist and vasodilating activities of the seven isomers

  摘要：

  Propranolol (Inderal; 1) is extensively metabolized in man. Metabolites of interest pharmacologically include ring-hydroxylated propranolols (1a-g). In order to identify these ring-oxidized products and to study the effect of hydroxyl position on biological activity, we have synthesized all seven isomers. With the exception of 1b and 1g, the desired compounds were prepared by alkylation of the respective methoxy-1-naphthols with epichlorohydrin and reaction of the resulting epoxide with isopropylamine. Cleavage og the methyl group in fused pyridine hydrochloride afforded 1a,c-f. 1g was prepared by the direct alkylation of 1,8-naphthalenediol (17) with epichlorohydrin, followed by reaction with isopropylamine. 1b was synthesized by treating 2-naphthol (9) with chlorine gas and then treating the resulting 1,1-dichloronaphthalen-2(1H)-one (10) with sodium allyl oxide. Acetylation of the hydroxy function and epoxidatrion of the allyl group, followed by relation with isopropylamine, gave 3'-hydroxy-4'-chloropropranolol (15). Dechlorination gave 1b. All of the racemic hydroxylated propranolols produced beta blockade and direct vasodilation in anesthetized dogs. The potency is strongly dependent upon the position of the hydroxyl group, i.e., 1e is 4 times as potent as 1 as a beta receptor antagonist, whereas 1a, 1b, and 1g are all significantly less potent than 1. For direct vasodilation, 1a and 1g are equipotent to 1, while 1b-f are much less potent. The potencies of the compounds were also compared with their 1-octanol/pH 7.4 buffer distribution coefficients; the direct vasodilating potency was found to increase with increasing lipophilicity, while the beta-adrenergic antagonist potency decreased.

  DOI：

  10.1021/jm00135a014

文献信息

• OATIS J. E. JR.; RUSSEL M. P.; KNAPP D. R.; WALLE T., J. MED. CHEM., 1981, 24, NO 3, 309-314
  作者：OATIS J. E. JR.、 RUSSEL M. P.、 KNAPP D. R.、 WALLE T.

  DOI：——

  日期：——
• Ring-hydroxylated propranolol: synthesis and .beta.-receptor antagonist and vasodilating activities of the seven isomers
  作者：J. E. Oatis、M. P. Russell、D. R. Knapp、T. Walle

  DOI：10.1021/jm00135a014

  日期：1981.3

  Propranolol (Inderal; 1) is extensively metabolized in man. Metabolites of interest pharmacologically include ring-hydroxylated propranolols (1a-g). In order to identify these ring-oxidized products and to study the effect of hydroxyl position on biological activity, we have synthesized all seven isomers. With the exception of 1b and 1g, the desired compounds were prepared by alkylation of the respective methoxy-1-naphthols with epichlorohydrin and reaction of the resulting epoxide with isopropylamine. Cleavage og the methyl group in fused pyridine hydrochloride afforded 1a,c-f. 1g was prepared by the direct alkylation of 1,8-naphthalenediol (17) with epichlorohydrin, followed by reaction with isopropylamine. 1b was synthesized by treating 2-naphthol (9) with chlorine gas and then treating the resulting 1,1-dichloronaphthalen-2(1H)-one (10) with sodium allyl oxide. Acetylation of the hydroxy function and epoxidatrion of the allyl group, followed by relation with isopropylamine, gave 3'-hydroxy-4'-chloropropranolol (15). Dechlorination gave 1b. All of the racemic hydroxylated propranolols produced beta blockade and direct vasodilation in anesthetized dogs. The potency is strongly dependent upon the position of the hydroxyl group, i.e., 1e is 4 times as potent as 1 as a beta receptor antagonist, whereas 1a, 1b, and 1g are all significantly less potent than 1. For direct vasodilation, 1a and 1g are equipotent to 1, while 1b-f are much less potent. The potencies of the compounds were also compared with their 1-octanol/pH 7.4 buffer distribution coefficients; the direct vasodilating potency was found to increase with increasing lipophilicity, while the beta-adrenergic antagonist potency decreased.