Pyrazinamide
Overview
Description
Pyrazinamide (PZA) is a first-line antitubercular drug critical for shortening tuberculosis (TB) treatment duration. Unlike most antibiotics, PZA requires acidic pH (5.5) for activity and is converted intracellularly to pyrazinoic acid (POA) via the enzyme pyrazinamidase (PZase). POA disrupts bacterial membrane energetics and inhibits targets like ribosomal protein S1 (RpsA) and fatty acid synthesis . PZA is uniquely effective against non-replicating, persistent Mycobacterium tuberculosis (Mtb), making it indispensable in combination therapies with rifampicin and isoniazid . Resistance arises primarily from mutations in the pncA gene, which encodes PZase, leading to reduced POA production .
Preparation Methods
Synthetic Routes and Reaction Conditions: Pyrazinamide can be synthesized through several methods:
2-Cyanopyrazine Hydration: This method involves the hydration of 2-cyanopyrazine to produce this compound.
2-Pyrazinecarboxamide Formation: Another method involves the reaction of pyrazine with formamide in the presence of hydrogen peroxide and ferrous sulfate to yield this compound.
2-Pyrazinecarboxylate Ammonolysis: This method uses 2-pyrazinecarboxylate, which undergoes ammonolysis in the presence of ammonia to form this compound.
Industrial Production Methods: The industrial production of this compound primarily relies on the hydration of 2-cyanopyrazine due to its high yield and scalability. This method involves the use of catalysts and controlled reaction conditions to ensure high purity and efficiency .
Types of Reactions:
Oxidation: this compound can undergo oxidation reactions, particularly in the presence of strong oxidizing agents.
Reduction: It can be reduced to its corresponding amine derivative under specific conditions.
Substitution: this compound can participate in substitution reactions, where the amide group can be replaced by other functional groups.
Common Reagents and Conditions:
Oxidizing Agents: Hydrogen peroxide, potassium permanganate.
Reducing Agents: Sodium borohydride, lithium aluminum hydride.
Substitution Reagents: Various alkylating agents and nucleophiles.
Major Products:
Oxidation Products: Pyrazine-2-carboxylic acid.
Reduction Products: Pyrazine-2-carboxamide.
Substitution Products: Various substituted pyrazine derivatives.
Scientific Research Applications
Pharmacokinetics and Pharmacodynamics
Pyrazinamide exhibits unique pharmacokinetic properties that contribute to its effectiveness. It is converted into its active form, pyrazinoic acid, which targets non-replicating Mycobacterium tuberculosis. Research has shown that this compound's sterilizing effect is enhanced when administered at higher doses, leading to improved treatment outcomes.
Key Findings:
- A study established an in vitro pharmacokinetic-pharmacodynamic model that demonstrated optimal dosing of this compound (15-30 mg/kg) achieved effective concentrations in only 15.1% to 53.3% of patients, suggesting higher doses (>60 mg/kg) may be necessary for better efficacy .
- Monte Carlo simulations indicated that higher maximum concentrations of this compound correlate with shorter time to culture conversion in TB patients .
Efficacy in Combination Therapies
This compound is often used in combination with other antitubercular agents such as rifampicin and isoniazid. Its role in enhancing the efficacy of fluoroquinolone-based regimens for multidrug-resistant TB has been documented.
Combination Therapy Insights:
- A study found that adding this compound to fluoroquinolone regimens significantly increased the incidence of early sputum culture conversion by 71%, highlighting its importance in treatment protocols for multidrug-resistant TB .
- In trials involving fixed-dose combinations, this compound has been shown to maintain bioavailability without negative interactions with other drugs, supporting its use in combination therapies .
Safety Profile and Hepatotoxicity
While this compound is effective, it is associated with hepatotoxicity, which can complicate treatment regimens. Studies have indicated that this compound may be more hepatotoxic than other first-line agents like isoniazid and rifampicin.
Safety Data:
- A retrospective cohort study reported a higher incidence of hepatotoxicity among patients treated with this compound compared to those receiving isoniazid and rifampicin alone .
- Monitoring liver function tests is recommended during treatment, especially in populations at risk for liver disease.
Case Studies
Several case studies have highlighted both the therapeutic benefits and adverse effects associated with this compound treatment.
Case Study Examples:
- Phototoxicity Reaction: A patient developed severe phototoxic rashes after starting a regimen including this compound. Discontinuation of the drug was necessary after attempts to desensitize were unsuccessful .
- Hepatotoxicity Incidents: A cohort analysis identified multiple cases where patients experienced significant liver enzyme elevations during therapy with regimens containing this compound, necessitating careful monitoring and potential regimen adjustments .
Data Summary Tables
| Study/Trial | Key Findings | Patient Population | Outcome |
|---|---|---|---|
| In vitro PK-PD Model | Higher doses improve efficacy | 10,000 simulated patients | Optimal AUC/MIC achieved only in a subset |
| Fluoroquinolone Combination | Increased early culture conversion | MDR-TB patients | 71% increase in treatment completion rates |
| Hepatotoxicity Analysis | Higher risk compared to other agents | 430 patients | Significant liver enzyme elevation noted |
Mechanism of Action
Pyrazinamide is a prodrug that is converted into its active form, pyrazinoic acid, by the enzyme pyrazinamidase within the bacterial cell. Pyrazinoic acid disrupts the bacterial cell membrane potential and interferes with fatty acid synthesis, leading to the death of Mycobacterium tuberculosis. The drug is more active at acidic pH levels, which are typically found within macrophages where the bacteria reside .
Comparison with Similar Compounds
Structural Analogs and Derivatives
Pyrazinamide’s pyrazine-2-carboxamide core has inspired derivatives with modified pharmacokinetic and activity profiles:
- Fluoroquinolone-Pyrazinamide Hybrids: Mannich base derivatives combining PZA with fluoroquinolones exhibit higher lipophilicity (log P = 1.8 vs. PZA’s 0.3) and enhanced activity against multidrug-resistant TB (MDR-TB) (MIC: 0.5–2.0 µg/mL vs. PZA’s 16–50 µg/mL) .
- N-Benzylpyrazinecarboxamides: Substituents like tert-butyl and methoxy groups improve activity against non-tuberculous mycobacteria (MIC: 8–32 µg/mL) resistant to PZA .
- Thiazolidinedione Derivatives : These compounds show comparable or superior in vitro activity (MIC: 1.56–25 µg/mL) to PZA (MIC: 50.77 µg/mL) .
Antimicrobial Activity and Efficacy
*MOTTs: Mycobacteria other than tuberculosis.
Pharmacokinetic and Pharmacodynamic Comparisons
- Bioavailability : PZA’s bioavailability in fixed-dose combinations (e.g., Trifazid) is comparable to standalone formulations (AUC: 350–400 µg·hr/mL) .
- Exposure-Response : Higher PZA Cmax correlates with faster culture conversion in TB patients, but efficacy depends on rifampicin co-administration (adjusted risk ratio: 1.38) .
- Lipophilicity: Derivatives like fluorquinolone-PZA hybrids (log P = 1.8) outperform PZA (log P = 0.3) in penetrating the lipid-rich Mtb cell wall .
Resistance Profiles and Mechanisms
- PZA Resistance: ~85% of resistant strains harbor pncA mutations, reducing PZase activity and POA production. Phenotypic testing is challenging due to pH-dependent activity .
- Cross-Resistance : PZA-resistant strains remain susceptible to analogs like N-benzyl derivatives, which bypass pncA-mediated activation .
Clinical Trial Outcomes and Combination Therapies
- MDR-TB Treatment: Adding PZA to fluoroquinolone regimens increases early culture conversion by 38% (risk ratio: 1.38) .
- Synergy with Rifampicin : PZA’s sterilizing effect reduces relapse rates in drug-susceptible TB when combined with rifampicin .
Computational and In Silico Studies
- Molecular Dynamics (MD) : 2-substituted benzyl derivatives (e.g., 4j) exhibit stable binding to Prolyl-tRNA synthetase due to reduced RMSF (0.2 Å vs. 1.5 Å in unsubstituted analogs) .
- Density Functional Theory (DFT) : this compound analogs with electron-withdrawing groups show higher reactivity indices (ΔN = 3.2 vs. PZA’s 2.8), correlating with improved bioactivity .
Biological Activity
Pyrazinamide (PZA) is a critical first-line medication used in the treatment of tuberculosis (TB). As a prodrug, it is converted into its active form, pyrazinoic acid (POA), which exerts its antibacterial effects primarily against Mycobacterium tuberculosis (Mtb) during the acidic conditions found in infected tissues. This article delves into the biological activity of this compound, highlighting its mechanisms of action, pharmacokinetics, clinical efficacy, and safety profile.
This compound's primary mechanism involves the inhibition of coenzyme A biosynthesis in M. tuberculosis by targeting the enzyme aspartate decarboxylase (PanD). Research indicates that POA binds to PanD, leading to its degradation by the caseinolytic protease ClpC1-ClpP, rather than merely inhibiting its function . This novel mechanism positions this compound as a target degrader, which is a promising strategy in drug discovery.
| Mechanism | Description |
|---|---|
| Prodrug Conversion | This compound → Pyrazinoic Acid (POA) |
| Target Enzyme | Aspartate Decarboxylase (PanD) |
| Action | Induces degradation of PanD via ClpC1-ClpP protease |
Pharmacokinetics
The pharmacokinetic parameters of this compound are crucial for optimizing its therapeutic efficacy. Studies have shown that higher concentrations of this compound correlate with improved culture conversion rates in TB patients. A population pharmacokinetic model demonstrated that dosing regimens significantly affect drug exposure and treatment outcomes .
Key Pharmacokinetic Findings
- Peak Concentration (Cmax) : Higher doses lead to increased Cmax and area under the curve (AUC), enhancing treatment effectiveness.
- Half-Life : The terminal elimination half-life of this compound averages around 9-10 hours.
- Bioavailability : The drug exhibits good bioavailability when administered in fixed-dose combinations with other TB medications like rifampicin and isoniazid .
Table 2: Pharmacokinetic Parameters
| Parameter | Value |
|---|---|
| Cmax | Varies with dosage |
| Half-Life | 9-10 hours |
| Bioavailability | High |
Clinical Efficacy
This compound plays a pivotal role in TB treatment regimens. It has been shown to enhance early culture conversion rates significantly. In a study involving multidrug-resistant TB (MDR-TB) patients, this compound use increased the incidence proportion of early culture conversion by approximately 38% compared to non-users .
Case Study: MDR-TB Treatment
In a cohort study involving 194 MDR-TB patients, those treated with fluoroquinolone-based regimens that included this compound demonstrated better outcomes than those who did not receive the drug. The adjusted risk ratio for early sputum culture conversion was notably higher among this compound users .
Safety Profile and Adverse Effects
While this compound is effective, it is associated with several adverse effects, most notably hepatotoxicity. A retrospective cohort study indicated that this compound is more hepatotoxic than other first-line TB drugs like isoniazid and rifampicin . Monitoring liver function during treatment is essential to mitigate risks.
Common Adverse Effects
- Hepatotoxicity : Increased liver enzyme levels leading to potential liver damage.
- Thrombocytopenia : A rare but reported side effect where platelet counts drop significantly .
- Gastrointestinal Disturbances : Nausea and vomiting are common complaints among patients.
Table 3: Adverse Effects of this compound
| Adverse Effect | Incidence Rate |
|---|---|
| Hepatotoxicity | Higher than isoniazid |
| Thrombocytopenia | Rare |
| Gastrointestinal Issues | Common |
Properties
IUPAC Name |
pyrazine-2-carboxamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
IPEHBUMCGVEMRF-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1=CN=C(C=N1)C(=O)N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C5H5N3O |
Source
|
| Record name | PYRAZINAMIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20970 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | pyrazinamide | |
| Source | Wikipedia | |
| URL | https://en.wikipedia.org/wiki/Pyrazinamide | |
| Description | Chemical information link to Wikipedia. | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID9021215 |
Source
|
| Record name | Pyrazinamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID9021215 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
123.11 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Pyrazinamide is a white powder. Sublimes from 318 °F. (NTP, 1992), Solid |
Source
|
| Record name | PYRAZINAMIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20970 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Pyrazinamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014483 | |
| 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 |
SUB (NTP, 1992) |
Source
|
| Record name | PYRAZINAMIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20970 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
Solubility |
>18.5 [ug/mL] (The mean of the results at pH 7.4), Soluble (NTP, 1992), Solubility (mg/ml, 25 °C): methanol 13.8; absolute ethanol 5.7; isopropanol 3.8; ether 1.0; isooctane 0.01; chloroform 7.4, In water, 15 mg/ml @ 25 °C, 9.37e+01 g/L |
Source
|
| Record name | SID8139959 | |
| Source | Burnham Center for Chemical Genomics | |
| URL | https://pubchem.ncbi.nlm.nih.gov/bioassay/1996#section=Data-Table | |
| Description | Aqueous solubility in buffer at pH 7.4 | |
| Record name | PYRAZINAMIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20970 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Pyrazinamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00339 | |
| 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 | PYRAZINAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3576 | |
| 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 | Pyrazinamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014483 | |
| 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. | |
Color/Form |
Crystals, Crystals from water or alcohol, Crystals from water or ethyl alcohol | |
CAS No. |
98-96-4 |
Source
|
| Record name | PYRAZINAMIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20970 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Pyrazinamide | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=98-96-4 | |
| 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 | Pyrazinamide [USP:INN:BAN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000098964 | |
| 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 | Pyrazinamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00339 | |
| 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 | pyrazinamide | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=757304 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | pyrazinamide | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=14911 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | 2-Pyrazinecarboxamide | |
| Source | EPA Chemicals under the TSCA | |
| URL | https://www.epa.gov/chemicals-under-tsca | |
| Description | EPA Chemicals under the Toxic Substances Control Act (TSCA) collection contains information on chemicals and their regulations under TSCA, including non-confidential content from the TSCA Chemical Substance Inventory and Chemical Data Reporting. | |
| Record name | Pyrazinamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID9021215 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Pyrazinamide | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.002.470 | |
| 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 | PYRAZINAMIDE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/2KNI5N06TI | |
| 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 | PYRAZINAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3576 | |
| 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 | Pyrazinamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014483 | |
| 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 |
376 to 379 °F (NTP, 1992), 192 °C |
Source
|
| Record name | PYRAZINAMIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20970 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
| Explanation | CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data. | |
| Record name | Pyrazinamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00339 | |
| 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 | PYRAZINAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3576 | |
| 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 | Pyrazinamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014483 | |
| 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 I
Procedure details
Synthesis routes and methods II
Procedure details
Synthesis routes and methods III
Procedure details
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.
One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.
Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.
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
Disclaimer and Information on In-Vitro Research Products
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.
