5-羟基普萘洛尔 | 81907-82-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 5-羟基普萘洛尔
• 中文别名: 1,3-二噁烷,2-苯基-5-丙基-
• 英文名称: 5-Hydroxypropranolol
• 英文别名: 5'-hydroxypropranolol；5-OHP；5-Hydroxy Propranolol；5-[2-hydroxy-3-(propan-2-ylamino)propoxy]naphthalen-1-ol
• CAS: 81907-82-6
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: WMYPGILKDMWISO-UHFFFAOYSA-N

物化性质

• 沸点：
  487.5±35.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：50 mg/ml； DMF:PBS(pH 7.2)(1:1)：0.5 mg/ml； DMSO：30 mg/ml；乙醇：30 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.7
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

代谢

5-羟基普萘洛尔是dexpropranolol（普萘洛尔）的人类已知代谢物。

5-Hydroxypropranolol is a known human metabolite of dexpropranolol (propranolol).

来源:NORMAN Suspect List Exchange

安全信息

• 储存条件：
  -20°C，密封保存于干燥处。

制备方法与用途

5-羟基普萘洛尔是普萘洛尔的代谢产物，而普萘洛尔是一种β-肾上腺素受体拮抗剂。

反应信息

• 作为反应物：
  描述：

  5-羟基普萘洛尔 、 盐酸 生成 5-[2-羟基-3-(异丙基氨基)丙氧基]萘-1-醇盐酸盐
  参考文献：
  名称：

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

  摘要：

  DOI：
• 作为产物：
  描述：

  普萘洛尔 在 formic acid oxidase from Aspergillus oryzae 、 氧气 、 sodium formate 、 维生素 C 作用下， 以 aq. phosphate buffer 为溶剂， 反应 3.0h， 以42%的产率得到5-羟基普萘洛尔
  参考文献：
  名称：

  米曲霉的甲酰氧化酶（FOx）：一种催化剂能够实现多种H2 O2依赖性的生物催化氧化反应。

  摘要：

  越来越多的生物催化氧化反应依赖于H 2 O 2作为清洁氧化剂。但是，大多数酶对H 2 O 2的鲁棒性差，因此需要更有效的原位H 2 O 2生成系统。与众所周知的甲酸脱氢酶促进NADH依赖的反应类似，我们在此提议采用甲酸氧化酶（FOx）促进H 2 O 2依赖的酶促氧化反应。即使在未优化的条件下，也可以实现FOx /过氧合酶催化的高周转率。

  DOI：

  10.1002/anie.201902380

文献信息

• Product Inhibition and Dose‐Dependent Bioavailability of Propranolol in the Isolated Perfused Rat Liver Preparation
  作者：Hany Ghabrial、Romina Nand、Cheryl K. Stead、Richard A. Smallwood、Denis J. Morgan

  DOI：10.1002/jps.2600830704

  日期：1994.7

  We investigated in the isolated perfused rat liver (IPRL) whether product inhibition of metabolism contributes to the dose-dependent bioavailability of propranolol, a drug with a high, but saturable, hepatic first-pass effect. (+/-)-Propranolol was infused in the IPRL, using a recirculating design, for three 36-min periods (n = 9). Mean steady-state reservoir, i.e. hepatic inflow concentrations (Cin)

  我们在离体灌流大鼠肝脏（IPRL）中研究了产品代谢的抑制作用是否对普萘洛尔具有剂量依赖性的生物利用度，普萘洛尔是一种具有较高但可饱和的肝首过效应的药物。使用再循环设计将（+/-）-普萘洛尔注入IPRL中，历时36分钟，共3次（n = 9）。平均稳态储库，即肝流入浓度（Cin）分别为4.97、10.4和20.4 microM。代谢产物4'-羟基普萘洛尔，5'-羟基普萘洛尔，N-去异丙基普萘洛尔和萘氧基乳酸（NLA）（一种主要的侧链氧化代谢物）的平均储库浓度随普萘洛尔剂量的增加而成比例增加，但它们的产率并未达到稳定州。在单独的实验（n = 4）中，灌注液含7.1、12.8和21。使用单程设计，分别使6 microM（+/-）-普萘洛尔分别对应于114、205和346 nmol / min的给药速率通过肝脏30分钟。在循环IPRL中，普萘洛尔的生物利用度（肝流出浓度/ Cin）随Cin从0.012增加到0
• Methods and compositions for modulating β-amyloid/α7-nAChR interactions
  申请人：Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

  公开号：US11382875B2

  公开（公告）日：2022-07-12

  Methods of modulating the interaction between β-amyloid and α7-nAChR are provided. Aspects of the methods include administering to the subject an effective amount of a naphthalene derivative active agent. Compositions and kits for practicing the subject methods are also provided. The methods, compositions and kits find use in treating a variety of applications, such as treating a subject for a neurodegenerative disease, e.g., Alzheimer's disease.

  本研究提供了调节β-淀粉样蛋白与α7-nAChR之间相互作用的方法。这些方法的各个方面包括向受试者施用有效量的萘衍生物活性剂。还提供了用于实施主体方法的组合物和试剂盒。这些方法、组合物和试剂盒可用于治疗各种应用，如治疗神经退行性疾病，如阿尔茨海默病。
• 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.
• Regioselective preparation of 5-hydroxypropranolol and 4′-hydroxydiclofenac with a fungal peroxygenase
  作者：Matthias Kinne、Marzena Poraj-Kobielska、Elisabet Aranda、René Ullrich、Kenneth E. Hammel、Katrin Scheibner、Martin Hofrichter

  DOI：10.1016/j.bmcl.2009.04.015

  日期：2009.6

  An extracellular peroxygenase of Agrocybe aegerita catalyzed the H2O2-dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol (1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol) and the non-steroidal anti-inflammatory drug diclofenac (2-[2-[(2,6-dichlorophenyl) amino]phenyl]acetic acid) to give the human drug metabolites 5-hydroxypropranolol (5-OHP) and 4'-hydroxydiclofenac (4'-OHD). The reactions proceeded regioselectively with high isomeric purity and gave the desired 5-OHP and 4'-OHD in yields up to 20% and 65%, respectively. O-18-labeling experiments showed that the phenolic hydroxyl groups in 5-OHP and 4'-OHD originated from H2O2, which establishes that the reaction is mechanistically a peroxygenation. Our results raise the possibility that fungal peroxygenases may be useful for versatile, cost-effective, and scalable syntheses of drug metabolites. (C) 2009 Elsevier Ltd. All rights reserved.
• US4029676A
  申请人：——

  公开号：US4029676A

  公开（公告）日：1977-06-14