普萘洛尔
概述
描述
普萘洛尔于 1962 年首次获得专利，并于 1964 年获准用于医疗 。普萘洛尔广泛用于治疗各种心血管疾病，例如高血压、心绞痛和心律失常。 此外，它还用于治疗焦虑症、预防偏头痛和治疗震颤 .
科学研究应用
普萘洛尔有广泛的科学研究应用：
作用机制
生化分析
Biochemical Properties
Propranolol plays a significant role in biochemical reactions by interacting with various enzymes, proteins, and other biomolecules. It primarily binds to beta-adrenergic receptors, inhibiting the action of catecholamines like adrenaline and noradrenaline. This interaction leads to a decrease in cyclic adenosine monophosphate (cAMP) levels, which in turn reduces the activity of protein kinase A (PKA). Propranolol also interacts with cytochrome P450 enzymes, particularly CYP2D6 and CYP1A2, which are involved in its metabolism .
Cellular Effects
Propranolol exerts various effects on different types of cells and cellular processes. In cardiac cells, it reduces heart rate and contractility by blocking beta-adrenergic receptors, leading to decreased calcium influx. In neuronal cells, propranolol can cross the blood-brain barrier and influence neurotransmitter release, thereby reducing anxiety and preventing migraines. Additionally, propranolol affects cell signaling pathways by inhibiting the cAMP-PKA pathway, which impacts gene expression and cellular metabolism .
Molecular Mechanism
The molecular mechanism of propranolol involves its binding to beta-adrenergic receptors, which prevents the activation of these receptors by catecholamines. This inhibition leads to a decrease in cAMP levels and subsequent reduction in PKA activity. Propranolol also inhibits the activity of certain cytochrome P450 enzymes, affecting its own metabolism and the metabolism of other drugs. Furthermore, propranolol can modulate gene expression by influencing transcription factors and other regulatory proteins .
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of propranolol change over time due to its stability and degradation. Propranolol is relatively stable under physiological conditions, but it can undergo degradation in the presence of light and heat. Long-term studies have shown that propranolol can have sustained effects on cellular function, including prolonged inhibition of beta-adrenergic receptors and persistent changes in gene expression. These effects are observed in both in vitro and in vivo studies .
Dosage Effects in Animal Models
The effects of propranolol vary with different dosages in animal models. At low doses, propranolol effectively reduces heart rate and blood pressure without significant adverse effects. At higher doses, propranolol can cause bradycardia, hypotension, and other toxic effects. Threshold effects have been observed, where a certain dosage is required to achieve the desired therapeutic effect. In animal studies, propranolol has been shown to affect various physiological parameters, including heart rate, blood pressure, and metabolic rate .
Metabolic Pathways
Propranolol is metabolized primarily in the liver through three main pathways: aromatic hydroxylation, N-dealkylation, and direct glucuronidation. The enzymes involved in these pathways include CYP2D6 and CYP1A2. The primary metabolites of propranolol are propranolol glucuronide, naphthyloxylactic acid, and sulfate and glucuronic acid conjugates of 4-hydroxy propranolol. These metabolites possess varying degrees of beta-adrenergic receptor blocking activity and can influence the overall pharmacological effects of propranolol .
Transport and Distribution
Propranolol is transported and distributed within cells and tissues through various mechanisms. It is highly lipophilic, allowing it to cross cell membranes easily and accumulate in tissues with high lipid content, such as the brain and adipose tissue. Propranolol is also transported by specific binding proteins and transporters, which facilitate its distribution within the body. The localization and accumulation of propranolol can affect its therapeutic efficacy and potential side effects .
Subcellular Localization
The subcellular localization of propranolol is influenced by its lipophilicity and interactions with cellular components. Propranolol can localize to various subcellular compartments, including the plasma membrane, mitochondria, and endoplasmic reticulum. Its activity and function can be affected by post-translational modifications and targeting signals that direct it to specific organelles. The subcellular localization of propranolol plays a crucial role in its overall pharmacological effects and therapeutic outcomes .
准备方法
普萘洛尔可以通过多种合成路线合成。一种常见的方法是让萘酚与环氧氯丙烷反应生成 3-(1-萘氧基)-1,2-环氧丙烷。 然后将此中间体与异丙胺反应生成普萘洛尔 。 该反应通常需要相转移催化剂和碱性介质来促进反应 。 工业生产方法通常涉及类似步骤，但针对大规模合成进行了优化，确保高产率和高纯度 .
化学反应分析
普萘洛尔经历各种化学反应，包括：
氧化： 普萘洛尔可以被氧化生成 4'-羟基普萘洛尔，这是一种主要的代谢产物.
还原： 还原反应不太常见，但在特定条件下会发生。
这些反应中常用的试剂包括高锰酸钾等氧化剂，硼氢化钠等还原剂，以及甲醇钠等亲核试剂 。形成的主要产物取决于所用反应条件和试剂。
相似化合物的比较
普萘洛尔与其他β受体阻滞剂，如美托洛尔、阿替洛尔和噻吗洛尔相比：
属性
IUPAC Name |
1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C16H21NO2/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16/h3-9,12,14,17-18H,10-11H2,1-2H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
AQHHHDLHHXJYJD-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC(C)NCC(COC1=CC=CC2=CC=CC=C21)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C16H21NO2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID6023525 |
Source
|
| Record name | Propranolol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6023525 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
259.34 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Solubility |
0.0617 mg/L at 25 °C |
Source
|
| Record name | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Mechanism of Action |
Propranolol is a nonselective β-adrenergic receptor antagonist. Blocking of these receptors leads to vasoconstriction, inhibition of angiogenic factors like vascular endothelial growth factor (VEGF) and basic growth factor of fibroblasts (bFGF), induction of apoptosis of endothelial cells, as well as down regulation of the renin-angiotensin-aldosterone system. |
Source
|
| Record name | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
CAS No. |
525-66-6, 13013-17-7 |
Source
|
| Record name | Propranolol | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=525-66-6 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | racemic-Propranolol | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000525666 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Propranolol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6023525 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | (±)-1-(isopropylamino)-3-(naphthyloxy)propan-2-ol | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.032.592 | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | Propranolol | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.007.618 | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | PROPRANOLOL | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/9Y8NXQ24VQ | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Melting Point |
96 °C |
Source
|
| Record name | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
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Retrosynthesis Analysis
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| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
体外研究产品的免责声明和信息
请注意，BenchChem 上展示的所有文章和产品信息仅供信息参考。 BenchChem 上可购买的产品专为体外研究设计，这些研究在生物体外进行。体外研究，源自拉丁语 "in glass"，涉及在受控实验室环境中使用细胞或组织进行的实验。重要的是要注意，这些产品没有被归类为药物或药品，他们没有得到 FDA 的批准，用于预防、治疗或治愈任何医疗状况、疾病或疾病。我们必须强调，将这些产品以任何形式引入人类或动物的身体都是法律严格禁止的。遵守这些指南对确保研究和实验的法律和道德标准的符合性至关重要。
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