Carbimazole
Overview
Description
Carbimazole is an antithyroid agent primarily used to treat hyperthyroidism and thyrotoxicosis. It is a pro-drug that is metabolized into methimazole, which is responsible for its antithyroid activity . This compound works by decreasing the uptake and concentration of inorganic iodine by the thyroid gland, thereby reducing the formation of thyroid hormones triiodothyronine (T3) and thyroxine (T4) .
Preparation Methods
Synthetic Routes and Reaction Conditions: Carbimazole can be synthesized through the reaction of ethyl 3-methyl-2-thioimidazoline-1-carboxylate with appropriate reagents under controlled conditions . The process involves the formation of a thioimidazoline ring, which is crucial for its biological activity.
Industrial Production Methods: In industrial settings, this compound is produced by optimizing the reaction conditions to ensure high yield and purity. This involves precise control of temperature, pH, and reaction time. The final product is then purified using techniques such as recrystallization and chromatography .
Chemical Reactions Analysis
Types of Reactions: Carbimazole undergoes various chemical reactions, including:
Oxidation: this compound can be oxidized to form methimazole, its active metabolite.
Reduction: Under certain conditions, this compound can be reduced to its corresponding thiol derivative.
Substitution: this compound can participate in substitution reactions, particularly involving the imidazole ring.
Common Reagents and Conditions:
Oxidation: Hydrogen peroxide (H2O2) or other oxidizing agents.
Reduction: Sodium borohydride (NaBH4) or lithium aluminum hydride (LiAlH4).
Substitution: Various nucleophiles under acidic or basic conditions.
Major Products:
Oxidation: Methimazole.
Reduction: Thiol derivatives.
Substitution: Various substituted imidazole derivatives.
Scientific Research Applications
Carbimazole has a wide range of applications in scientific research:
Mechanism of Action
Carbimazole exerts its effects by inhibiting the thyroid peroxidase enzyme, which is essential for the iodination and coupling of tyrosine residues on thyroglobulin . This inhibition reduces the production of thyroid hormones T3 and T4. Once absorbed, this compound is rapidly converted to methimazole, which is the active form responsible for its antithyroid activity .
Comparison with Similar Compounds
Methimazole: The active metabolite of carbimazole, used directly in some regions.
Propylthiouracil: Another antithyroid drug used to treat hyperthyroidism.
Comparison:
Methimazole vs. This compound: Methimazole is the active form of this compound. While this compound is a pro-drug, methimazole is administered directly in some regions.
Propylthiouracil vs. This compound: Both drugs inhibit thyroid hormone synthesis, but propylthiouracil also inhibits the peripheral conversion of T4 to T3.
This compound’s unique feature is its conversion to methimazole, allowing for a more controlled release of the active compound .
Properties
IUPAC Name |
ethyl 3-methyl-2-sulfanylideneimidazole-1-carboxylate |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C7H10N2O2S/c1-3-11-7(10)9-5-4-8(2)6(9)12/h4-5H,3H2,1-2H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
CFOYWRHIYXMDOT-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCOC(=O)N1C=CN(C1=S)C |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C7H10N2O2S |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID9022736 |
Source
|
| Record name | Carbimazole | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID9022736 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
186.23 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 | Carbimazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014533 | |
| 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 |
3.14e+00 g/L |
Source
|
| Record name | Carbimazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014533 | |
| 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 |
Carbimazole is an aitithyroid agent that decreases the uptake and concentration of inorganic iodine by thyroid, it also reduces the formation of di-iodotyrosine and thyroxine. Once converted to its active form of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4. |
Source
|
| Record name | Carbimazole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00389 | |
| 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. |
22232-54-8 |
Source
|
| Record name | Carbimazole | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=22232-54-8 | |
| 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 | Carbimazole [INN:BAN:DCF] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0022232548 | |
| 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 | Carbimazole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00389 | |
| 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 | Carbimazole | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=758966 | |
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| Record name | Carbimazole | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID9022736 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Carbimazole | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.040.762 | |
| 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. | |
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| Record name | CARBIMAZOLE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/8KQ660G60G | |
| 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 | Carbimazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014533 | |
| 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 |
123.5 °C |
Source
|
| Record name | Carbimazole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00389 | |
| 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 | Carbimazole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014533 | |
| 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. | |
Retrosynthesis Analysis
AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| 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
Q1: How does Carbimazole exert its antithyroid effect?
A1: this compound itself is a prodrug, rapidly metabolized into Methimazole, the active antithyroid agent. Methimazole acts by inhibiting thyroid peroxidase, a key enzyme involved in thyroid hormone synthesis. [, ]
Q2: Can you elaborate on the role of thyroid peroxidase in thyroid hormone production?
A2: Thyroid peroxidase catalyzes the iodination of tyrosine residues within thyroglobulin, a precursor protein. This iodination is essential for the formation of the thyroid hormones Triiodothyronine (T3) and Thyroxine (T4). [, ]
Q3: What are the downstream consequences of inhibiting thyroid peroxidase?
A3: By inhibiting thyroid peroxidase, Methimazole disrupts the production of T3 and T4, leading to a decrease in circulating thyroid hormone levels. This effectively reduces thyroid gland activity, hence its use in treating hyperthyroidism. [, , , ]
Q4: What is the molecular formula and weight of this compound?
A4: this compound has the molecular formula C7H10N2O2S and a molecular weight of 186.23 g/mol. []
Q5: Is there any spectroscopic data available for this compound?
A5: Yes, this compound can be analyzed using various spectroscopic techniques, including UV-Vis spectrophotometry. It exhibits a characteristic absorbance peak around 291 nm. []
Q6: What is known about the stability of this compound in different formulations?
A6: The stability of this compound can be influenced by factors like pH, temperature, and excipients used in formulations. Research is ongoing to develop stable and bioavailable formulations, including controlled-release tablets. [, , ]
Q7: Have there been any computational studies on this compound?
A8: Yes, computational chemistry techniques like QSAR (Quantitative Structure-Activity Relationship) modeling have been employed to investigate the relationship between the structure of this compound analogs and their antithyroid activity. [, ]
Q8: How do structural modifications of this compound impact its antithyroid activity?
A9: Studies exploring the SAR of this compound analogs have revealed that specific structural features are crucial for its interaction with thyroid peroxidase and its inhibitory activity. Modifications to these key regions can significantly alter its potency and selectivity. [, , ]
Q9: What are the challenges in formulating stable this compound products?
A10: this compound's stability can be affected by various factors. Formulation scientists are continuously exploring strategies to overcome these challenges and develop formulations that ensure its stability, solubility, and bioavailability, such as controlled-release tablets for once-daily dosing in cats. [, , ]
Q10: Are there specific SHE (Safety, Health, and Environment) regulations regarding this compound handling and disposal?
A11: Yes, due to its pharmacological activity and potential environmental impact, this compound handling and disposal are subject to specific SHE regulations. Researchers and manufacturers must adhere to strict guidelines to minimize risks and ensure responsible practices. [, ]
Q11: What is the ADME profile of this compound?
A12: this compound is rapidly absorbed after oral administration and extensively metabolized, primarily in the liver, to its active form, Methimazole. It is then excreted mainly in urine. [, ]
Q12: How do food intake and other factors influence the pharmacokinetics of this compound?
A13: Studies have shown that food intake can enhance the absorption of this compound. Other factors like age, liver function, and concurrent medications can also influence its pharmacokinetic parameters. []
Q13: What in vitro models are used to study the effects of this compound?
A14: Cell-based assays utilizing thyroid cell lines are employed to investigate the direct effects of this compound and Methimazole on thyroid hormone synthesis and cell proliferation. [, ]
Q14: What animal models are relevant for studying this compound's effects?
A15: Rodent models, particularly rats, are commonly used to study the in vivo effects of this compound on thyroid function, morphology, and potential toxicity. [, , , , , , , , ]
Q15: Are there known mechanisms of resistance to this compound?
A16: While resistance to this compound is considered rare, factors like non-compliance with treatment and individual variability in drug metabolism can influence its effectiveness. [, ]
Q16: What are the known adverse effects associated with this compound use?
A17: While generally considered safe, this compound can cause side effects. For detailed information on potential adverse effects, please consult relevant medical literature and prescribing information. [, , , , , , , , , ]
Q17: Are there efforts to develop targeted drug delivery systems for this compound?
A18: Researchers are exploring innovative drug delivery approaches, such as transdermal formulations, to improve patient compliance and potentially reduce systemic side effects. []
Q18: Are there any biomarkers to monitor this compound treatment response?
A19: Thyroid function tests, including serum levels of T3, T4, and TSH, are routinely used to monitor treatment response and adjust this compound dosage. [, , , ]
Q19: What analytical methods are used to quantify this compound and Methimazole?
A20: High-Performance Liquid Chromatography (HPLC) coupled with various detection methods, such as UV-Vis spectrophotometry, is widely used for the accurate quantification of this compound and Methimazole in biological samples and pharmaceutical formulations. [, ]
Q20: How do the dissolution properties of this compound formulations affect its bioavailability?
A22: The dissolution rate of this compound tablets significantly influences its absorption and therapeutic efficacy. Different formulations, including controlled-release systems, are designed to optimize its dissolution profile and bioavailability. []
Q21: What quality control measures are implemented in this compound manufacturing?
A24: Stringent quality control measures are employed throughout the manufacturing process, from raw material sourcing to final product release, to ensure the consistency, safety, and efficacy of this compound. []
Q22: Can this compound elicit immunological responses?
A25: While uncommon, this compound can potentially induce immunological responses, including hypersensitivity reactions. Monitoring for such responses is crucial during therapy. []
Q23: Does this compound interact with drug transporters?
A26: Research suggests that this compound may interact with specific drug transporters, influencing its absorption, distribution, and elimination. Further studies are needed to elucidate the clinical relevance of these interactions. []
Q24: What is known about the biocompatibility of this compound?
A28: Studies have focused on assessing the potential toxicity of this compound, particularly in relation to its effects on various organs. While generally considered safe at therapeutic doses, adverse effects can occur. []
Q25: Are there alternative treatments for conditions where this compound is used?
A29: Yes, other antithyroid drugs like Propylthiouracil are available. The choice of treatment depends on individual patient factors and clinical judgment. Radioactive iodine therapy and surgery are also options for certain cases. [, , ]
Q26: Are there specific guidelines for the recycling and disposal of this compound?
A30: As with many pharmaceuticals, improper disposal of this compound can contribute to environmental contamination. Proper waste management practices and potential recycling strategies are essential to minimize its ecological impact. []
Q27: What research infrastructure and resources are important for this compound research?
A31: Advanced analytical techniques like HPLC and mass spectrometry, cell culture facilities, and animal models are essential for ongoing this compound research. Collaborative efforts and data sharing platforms facilitate scientific advancements in this field. []
Q28: What are some key milestones in the history of this compound research?
A32: The discovery of this compound and its subsequent introduction as an antithyroid therapy marked a significant advancement in the treatment of hyperthyroidism. Ongoing research continues to optimize its use and explore new therapeutic applications. []
Q29: How does this compound research intersect with other scientific disciplines?
A33: this compound research involves a multidisciplinary approach, integrating knowledge from endocrinology, pharmacology, medicinal chemistry, toxicology, and environmental science. This collaborative approach drives innovation and comprehensive understanding. []
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