Bisoprolol
Overview
Description
Bisoprolol is a cardioselective beta-1 adrenergic blocking agent, commonly known as a beta-blocker. It is primarily used to manage cardiovascular diseases such as high blood pressure, angina, and heart failure. This compound works by reducing the heart rate and the force of contraction, thereby lowering blood pressure and reducing the heart’s oxygen demand .
Preparation Methods
Bisoprolol can be synthesized through several methods. One common synthetic route involves the reaction of 4-isopropoxyethoxy methyl phenol with epichlorohydrin to form 2-[4-(2-isopropoxyethoxy)methyl]phenoxymethyl oxirane. This intermediate is then reacted with isopropylamine to yield this compound . Industrial production methods often involve similar steps but are optimized for large-scale production, ensuring high yield and purity .
Chemical Reactions Analysis
Bisoprolol undergoes various chemical reactions, including:
Oxidation: this compound can be oxidized to form various metabolites.
Reduction: Reduction reactions are less common but can occur under specific conditions.
Substitution: this compound can undergo substitution reactions, particularly involving its phenolic and amine groups.
Common reagents used in these reactions include oxidizing agents like hydrogen peroxide and reducing agents like sodium borohydride. The major products formed from these reactions are typically metabolites that are either excreted or further metabolized in the body .
Scientific Research Applications
Pharmaceutical Applications
1.1 Drug Delivery Systems
The amphiphilic nature of 2-Methylene-beta-alanine allows it to form micelles and liposomes, which are effective in encapsulating hydrophobic drugs. This enhances the solubility and bioavailability of these compounds, making them more effective in therapeutic applications. The ability to modify drug release profiles through the use of this compound can lead to improved patient outcomes in various treatments.
1.2 Antioxidant Properties
While 2-Methylene-beta-alanine itself does not exhibit antioxidant properties, it contributes to increased levels of carnosine in tissues. Carnosine is known for its ability to scavenge reactive oxygen species (ROS), thereby potentially mitigating oxidative stress and enhancing cellular protection against damage caused by free radicals.
Sports Nutrition
2.1 Performance Enhancement
Research indicates that supplementation with beta-alanine can enhance athletic performance by increasing muscle carnosine content. This results in improved buffering capacity during high-intensity exercise, which can delay fatigue and enhance endurance. A study on recreationally trained men demonstrated that a sustained-release formulation of beta-alanine improved performance metrics and reduced symptoms of paraesthesia commonly associated with beta-alanine supplementation .
2.2 Case Study: Equestrian Performance
In a study involving Yili horses participating in speed racing, beta-alanine supplementation resulted in a significant improvement in performance, with test group horses completing races faster than control group horses. The supplementation also led to increased levels of antioxidants in the blood, suggesting a dual benefit of enhanced performance and reduced oxidative stress during exercise .
Biochemical Research
3.1 Modulation of Enzymatic Activity
2-Methylene-beta-alanine has been studied for its potential to modulate the activity of various enzymes, including cytochrome c oxidase. Research indicates that increasing concentrations of this compound can significantly decrease enzyme function, suggesting applications in metabolic disorders where modulation of mitochondrial respiration is desired.
3.2 Biosynthesis of Natural Products
The incorporation of beta-amino acids like 2-Methylene-beta-alanine into natural products is an area of active research. The ability to swap beta-amino acid moieties with different side chains could lead to the development of novel bioactive compounds with therapeutic potential .
Summary Table of Applications
Mechanism of Action
Bisoprolol exerts its effects by selectively blocking beta-1 adrenergic receptors in the heart. This action reduces the heart rate and the force of contraction, leading to a decrease in cardiac output and blood pressure. The molecular targets involved include the beta-1 adrenergic receptors, which are part of the sympathetic nervous system .
Comparison with Similar Compounds
Bisoprolol is often compared with other beta-blockers such as atenolol, metoprolol, and propranolol. While all these compounds share a similar mechanism of action, this compound is unique in its high selectivity for beta-1 adrenergic receptors, which reduces the risk of side effects related to beta-2 receptor blockade, such as bronchoconstriction .
Similar Compounds
- Atenolol
- Metoprolol
- Propranolol
- Carvedilol
- Labetalol
This compound’s selectivity for beta-1 receptors makes it particularly suitable for patients with respiratory conditions like asthma, as it minimizes the risk of bronchospasm .
Biological Activity
Bisoprolol is a selective beta-1 adrenergic antagonist primarily used in the management of hypertension and heart failure. Its pharmacological properties, mechanisms of action, and clinical efficacy have been extensively studied, revealing significant insights into its biological activity. This article delves into the biological activity of this compound, supported by data tables, case studies, and detailed research findings.
This compound exhibits its therapeutic effects through competitive inhibition of beta-1 adrenergic receptors located predominantly in the heart. By blocking these receptors, this compound reduces cardiac output and lowers heart rate, which decreases myocardial oxygen demand. Additionally, it is believed to lower renin secretion from the kidneys, further contributing to its antihypertensive effects .
Pharmacokinetics
The pharmacokinetics of this compound are characterized by moderate lipophilicity and high bioavailability. It is primarily metabolized in the liver via cytochrome P450 enzymes, particularly CYP2D6 and CYP3A4. Variations in these enzymes due to genetic polymorphisms can influence this compound's plasma concentrations and therapeutic outcomes .
Heart Failure
The Cardiac Insufficiency this compound Study II (CIBIS-II) demonstrated that this compound significantly reduces mortality in patients with chronic heart failure. Key findings include:
- All-Cause Mortality : A relative reduction of 29.3% compared to placebo (hazard ratio 0.66; 95% CI 0.54–0.81) was observed .
- Sudden Death : Fewer sudden deaths occurred in the this compound group (3.6% vs. 6.3% in placebo) with a hazard ratio of 0.56 .
Table 1: Summary of CIBIS-II Findings
| Outcome | This compound Group | Placebo Group | Hazard Ratio (95% CI) |
|---|---|---|---|
| All-Cause Mortality | 156 (11.8%) | 228 (17.3%) | 0.66 (0.54–0.81) |
| Sudden Death | 48 (3.6%) | 83 (6.3%) | 0.56 (0.39–0.80) |
| Hospitalization for HF | Reduced | Increased | - |
Hypertension
In patients with mild to moderate hypertension, this compound has shown significant reductions in blood pressure and heart rate:
- Blood Pressure Reduction : After six weeks of treatment, systolic blood pressure decreased by an average of 14.3 mmHg and diastolic by 8.4 mmHg .
- Heart Rate Reduction : The average reduction in heart rate was noted to be approximately 6 BPM .
BISOCOR Observational Study
This study evaluated the long-term effects of this compound on patients with heart failure over nine months:
- Ejection Fraction Improvement : An increase of 0.06 in ejection fraction was recorded.
- Adverse Effects : Approximately 10% of patients discontinued due to adverse effects, indicating a need for careful monitoring during treatment .
This compound in COPD Study (BICS)
A recent randomized clinical trial assessed this compound's efficacy in patients with chronic obstructive pulmonary disease (COPD):
Properties
IUPAC Name |
1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C18H31NO4/c1-14(2)19-11-17(20)13-23-18-7-5-16(6-8-18)12-21-9-10-22-15(3)4/h5-8,14-15,17,19-20H,9-13H2,1-4H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
VHYCDWMUTMEGQY-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=C(C=C1)COCCOC(C)C)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C18H31NO4 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID6022682 |
Source
|
| Record name | Bisoprolol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6022682 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
325.4 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 | Bisoprolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014750 | |
| 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. | |
Boiling Point |
445.0±45.0 |
Source
|
| Record name | Bisoprolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00612 | |
| 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) | |
Solubility |
7.07e-02 g/L |
Source
|
| Record name | Bisoprolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014750 | |
| 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 |
Though the mechanism of action of bisoprolol has not been fully elucidated in hypertension, it is thought that therapeutic effects are achieved through the antagonism of β-1adrenoceptors to result in lower cardiac output. Bisoprolol is a competitive, cardioselective β1-adrenergic antagonist. When β1-receptors (located mainly in the heart) are activated by adrenergic neurotransmitters such as epinephrine, both the blood pressure and heart rate increase, leading to greater cardiovascular work, increasing the demand for oxygen. Bisoprolol reduces cardiac workload by decreasing contractility and the need for oxygen through competitive inhibition of β1-adrenergic receptors. Bisoprolol is also thought to reduce the output of renin in the kidneys, which normally increases blood pressure. Additionally, some central nervous system effects of bisoprolol may include diminishing sympathetic nervous system output from the brain, decreasing blood pressure and heart rate. |
Source
|
| Record name | Bisoprolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00612 | |
| 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. |
66722-44-9 |
Source
|
| Record name | Bisoprolol | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=66722-44-9 | |
| 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 | Bisoprolol [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0066722449 | |
| 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 | Bisoprolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00612 | |
| 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 | Bisoprolol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6022682 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | 2-Propanol, 1-[4-[[2-(1-methylethoxy)ethoxy]methyl]phenoxy]-3-[(1-methylethyl)amino] | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.108.941 | |
| 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 | BISOPROLOL | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/Y41JS2NL6U | |
| 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 | Bisoprolol | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/8316 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
| Record name | Bisoprolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014750 | |
| 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 |
100-103, 100 °C |
Source
|
| Record name | Bisoprolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00612 | |
| 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 | Bisoprolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014750 | |
| 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. | |
Synthesis routes and methods
Procedure details
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
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| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
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Please be aware that all articles and product information presented on BenchChem are intended solely for informational purposes. The products available for purchase on BenchChem are specifically designed for in-vitro studies, which are conducted outside of living organisms. In-vitro studies, derived from the Latin term "in glass," involve experiments performed in controlled laboratory settings using cells or tissues. It is important to note that these products are not categorized as medicines or drugs, and they have not received approval from the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. We must emphasize that any form of bodily introduction of these products into humans or animals is strictly prohibited by law. It is essential to adhere to these guidelines to ensure compliance with legal and ethical standards in research and experimentation.
