4-甲氧基普萘洛尔 | 18507-09-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 4-甲氧基普萘洛尔
• 英文名称: 4-Methoxypropranolol
• 英文别名: 1-(4'-Methoxy-1'-naphthoxy)-3-(isopropylamino)-2-propanol；4-Methoxy Propranolol；1-(4-methoxynaphthalen-1-yl)oxy-3-(propan-2-ylamino)propan-2-ol
• CAS: 18507-09-0
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: OWXOFAQEGCLAOX-UHFFFAOYSA-N

物化性质

• 熔点：
  98-100?C
• 沸点：
  467.6±35.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)
• 溶解度：
  二氯甲烷、DMSO、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：

  4-甲氧基普萘洛尔 在 吡啶盐酸盐 作用下， 反应 1.0h， 生成 4-hydroxypropranolol
  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：

  4-甲氧基-1-萘酚 在 sodium hydroxide 作用下， 反应 14.0h， 生成 4-甲氧基普萘洛尔
  参考文献：
  名称：

  4-甲氧基普萘洛尔的合成，一种适用于通过 HPLC 测定普萘洛尔和 4-羟基普萘洛尔的内标

  摘要：

  描述了4-甲氧基心得安的合成。中间体和最终产品的结构通过通常的光谱方法得到保证。

  DOI：

  10.1002/ardp.19813140510

文献信息

• .beta.-Adrenergic blocking agents. II. Propranolol and related 3-amino-1-naphthoxy-2-propanols
  作者：A. F. Crowther、L. H. Smith

  DOI：10.1021/jm00311a021

  日期：1968.9
• 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：——
• REMON J.-P.; GYSELINCK P.; SYNAVE R.; SEVEREN R. VAN; BRAECKMANN P., ARCH. PHARM., 1981, 314, NO 5, 432-435
  作者：REMON J.-P.、 GYSELINCK P.、 SYNAVE R.、 SEVEREN R. VAN、 BRAECKMANN P.

  DOI：——

  日期：——
• Complete Reaction Phenotyping of Propranolol and 4-Hydroxypropranolol with the 19 Enzymes of the Human UGT1 and UGT2 Families
  作者：Fan Yang、Sijie Liu、Gerhard Wolber、Matthias Bureik、Maria Kristina Parr

  DOI：10.3390/ijms23137476

  日期：——

  Propranolol is a competitive non-selective beta-receptor antagonist that is available on the market as a racemic mixture. In the present study, glucuronidation of propranolol and its equipotent phase I metabolite 4-hydroxypropranolol by all 19 members of the human UGT1 and UGT2 families was monitored. UGT1A7, UGT1A9, UGT1A10 and UGT2A1 were found to glucuronidate propranolol, with UGT1A7, UGT1A9 and UGT2A1 mainly acting on (S)-propranolol, while UGT1A10 displays the opposite stereoselectivity. UGT1A7, UGT1A9 and UGT2A1 were also found to glucuronidate 4-hydroxypropranolol. In contrast to propranolol, 4-hydroxypropranolol was found to be glucuronidated by UGT1A8 but not by UGT1A10. Additional biotransformations with 4-methoxypropanolol demonstrated different regioselectivities of these UGTs with respect to the aliphatic and aromatic hydroxy groups of the substrate. Modeling and molecular docking studies were performed to explain the stereoselective glucuronidation of the substrates under study.
• 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.