Pyrazinamide

Base Information

• Chemical Name: Pyrazinamide
• CAS No.: 98-96-4
• Molecular Formula: C5H5N3O
• Molecular Weight: 123.114
• Hs Code.: 29339990
• European Community (EC) Number: 202-717-6
• NSC Number: 757304,14911
• UNII: 2KNI5N06TI
• DSSTox Substance ID: DTXSID9021215
• Nikkaji Number: J3.990J
• Wikipedia: Pyrazinamide
• Wikidata: Q417571
• NCI Thesaurus Code: C29395
• RXCUI: 8987
• Metabolomics Workbench ID: 42717
• ChEMBL ID: CHEMBL614
• Mol file: 98-96-4.mol

Synonyms:Pyrazinamide (TN);Pirazinamid;Pirazimida;D-50;T 165;Novamid;NCI-C01785;Pyrazineamide;MK 56;2-Carbamylpyrazine;D-50 (VAN);Pirazinamida [INN-Spanish];Pirazinamide [DCIT];PZA;2-Pyrazinecarboxamide;1/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9;Pyrazinamide (JP14/USP);5-25-04-00178 (Beilstein Handbook Reference);Prestwick_811;Zinamide;Pyrazinamidum [INN-Latin];PYZ;Pyrazinecarboxylic acid amide;Aldinamide;Pyrazinamide [BAN:INN:JAN];Unipyranamide;Pyrazinoic acid amide;DRG 0124;Aldinamid;Farmizina;Eprazin;pyrazine-2-carboxamide;Tebrazid;Pyrazine carboxylamide;Pyrazine carboxamide;

Chemical Property of Pyrazinamide

Chemical Property:

• Appearance/Colour: crystalline solid
• Melting Point: 189-191 °C(lit.)
• Refractive Index: 1.5900 (estimate)
• Boiling Point: 357.4 °C at 760 mmHg
• PKA: 0.5(at 25℃)
• Flash Point: 169.9 °C
• PSA: 68.87000
• Density: 1.301 g/cm³
• LogP: 0.27580
• Storage Temp.: -20°C Freezer
• Solubility.: H2O: soluble50mg/mL
• Water Solubility.: 15 mg/mL
• XLogP3: -0.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 123.043261792
• Heavy Atom Count: 9
• Complexity: 115

Purity/Quality:

≥99.0% ^*data from raw suppliers

Pyrazinamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): F,C
• Hazard Codes: F,C
• Statements: 11-34
• Safety Statements: 22-24/25-45-36/37/39-26-16

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antituberculosis Agents
• Canonical SMILES: C1=CN=C(C=N1)C(=O)N
• Recent ClinicalTrials: A Randomised Trial to Evaluate Toxicity and Efficacy of 1200mg and 1800mg Rifampicin for Pulmonary Tuberculosis
• Recent EU Clinical Trials: Randomized prospective phase II clinical trial investigating pharmacokinetics and safety aspects of higher doses of rifampicin and pyrazinamide in an shortened tuberculosis treatment compared to standartd treatment for a group of patients with mild to moderate active tuberculosis.
• Drug Interactions: 1, when being combined with allopurinol, colchicine, probenecid, and sulfinpyrazone, pyrazinamide can increase the serum uric acid concentration and further reduce the efficacy of the above drugs on gout. Therefore, when being combined with pyrazinamide, the above drugs should be subject to dose adjustment in order to control hyperuricemia and gout. 2, it can enhance the adverse reactions when combined with B sulfur isonicotinoyl amine. 3, when cyclosporine is used simultaneously with pyrazinamide, the blood concentration of the former drug may be reduced, and therefore the blood concentration needs to be monitored and we should adjust the dose if necessary. 4, it has synergistic effect when combined with isoniazid and rifampin and can delay the development of drug resistance. The above information is edited by the lookchem of Dai Xiongfeng.
• Indications: It can be used in combination with other anti-TB drugs for the treatment of tuberculosis that failed to be cured by first-line anti-TB drugs (such as streptomycin, isoniazid, rifampicin and ethambutol). This product is only valid against mycobacteria. In the past, pyrazinamide was used as second-line drugs, commonly applied to the patients undergoing retirement due to failure to be cured by other anti-TB drugs. A large number of clinical studies have shown: the short course regimen containing this product is suitable for being applied to the newly diagnosed sputum-positive cases. It is generally applied for 2 to 3 months. This protocol can enable a significant reduction of the re-positive rate of Mycobacterium tuberculosis after the end of treatment. This product has been well considered as the composition of triple or quadruple protocols in short course chemotherapy. Pyrazinamide is a synthetic analogue of nicotinamide. Its exact mechanism of action is not known, although its target appears to be the mycobacterial fatty acid synthetase involved in mycolic acid biosynthesis. Pyrazinamide requires an acidic environment, such as that found in the phagolysosomes, to express its tuberculocidal activity. Thus, pyrazinamide is highly effective on intracellular mycobacteria. The mycobacterial enzyme pyrazinamidase converts pyrazinamide to pyrazinoic acid, the active form of the drug.A mutation in the gene (pncA) that encodes pyrazinamidase is responsible for drug resistance; resistance can be delayed through the use of drug combination therapy.
• Uses: It is a kind of anti-tuberculosis drugs. An antibacterial agent used to study liver toxicity prevention Pyrazinamide is used therapeutically as an antitubercular agent. Pyrazinamide is used to form polymeric copper complexes, create pyrazine carboxamide scaffolds useful as FXs inhibitors, and as a component of mycobacteria identification kits. It is used to study liver toxicity prevention and mechanisms of resistance .
• Description: Pyrazinamide was synthesized in 1952, and it is the nitrogen-analog of nicotinamide. It exhibits hepatotoxicity. Synonyms of this drug are dexambutol, miambutol, esnbutol, ebutol, and others.
• Clinical Use: Tuberculosis (a component of the early, intensive phase of short-course therapy) Pyrazinamide is an essential component of the multidrug short-term therapy of tuberculosis. In combination with isoniazid and rifampin, it is active against the intracellular organisms that may cause relapse.
• Drug interactions: Potentially hazardous interactions with other drugs Ciclosporin: on limited evidence, pyrazinamide appears to reduce ciclosporin levels.

Technology Process of Pyrazinamide

There total 25 articles about Pyrazinamide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

2-pyrazine carbonitrile (19847-12-2) → pyrazinamide (98-96-4)

Guidance literature:

With manganese(IV) oxide; silica gel; In chlorobenzene; for 5h; Heating;

Reference yield: 100.0%

(1H-benzo[d][1,2,3]triazol-1-yl)(pyrazin-2-yl)methanone (306990-94-3) → pyrazinamide (98-96-4)

Guidance literature:

With ammonium hydroxide; In tetrahydrofuran; ethanol; at 20 ℃; for 4h;

DOI:10.1021/jo000792f

Reference yield: 95.2%

2-Methylpyrazine (109-08-0) → pyrazinamide (98-96-4)

Guidance literature:

With ammonium hydroxide; air; V₂O₅#dotMoO₃; at 390 ℃;

DOI:10.1007/BF00773004

upstream raw materials:

methyl pyrazine-2-carboxylate

3-amidecarbonylpyrazine-2-carboxylic acid

2,3-dicarboxypyrazine

urea

Downstream raw materials:

2-pyrazylcarboxylic acid

pyrazine-2-carbothioamide

5-(pyrazin-2-yl)-1,3,4-oxathiazol-2-one

Refernces

• 1、 Cheng, Zhongyi,Jiang, Shijin,Zhou, Zhemin. "Substrate access tunnel engineering for improving the catalytic activity of a thermophilic nitrile hydratase toward pyridine and pyrazine nitriles". . p. 8 - 13. Retrieved 2021/08/30.
• 2、 Vyas, Komal M.,Mandal, Poulami,Singh, Rinky,Mobin, Shaikh M.,Mukhopadhyay, Suman. "Arene-ruthenium(II)-phosphine complexes: Green catalysts for hydration of nitriles under mild conditions". . . Retrieved 2019/12/11.