Identification

Name
Pyrazinamide
Accession Number
DB00339  (APRD01206)
Type
Small Molecule
Groups
Approved
Description

A pyrazine that is used therapeutically as an antitubercular agent.

Structure
Thumb
Synonyms
  • 2-carbamylpyrazine
  • 2-pyrazinecarboxamide
  • Aldinamide
  • Pirazinamida
  • Pirazinamide
  • Pyrazinamid
  • Pyrazinamida
  • Pyrazinamide
  • Pyrazinamidum
  • Pyrazine carboxamide
  • pyrazine-2-carboxamide
  • Pyrazineamide
  • Pyrazinecarboxamide
  • Pyrazinoic acid amide
  • Pyrizinamide
External IDs
D-50 / MK-56 / NSC-14911 / PZA / Z
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pdp-pyrazinamideTablet500 mgOralPendopharm Division Of De Pharmascience Inc1984-12-31Not applicableCanada
Tebrazid Tab 500mgTablet500 mgOralValeant Canada Lp Valeant Canada S.E.C.1973-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PyrazinamideTablet500 mg/1OralA S Medication Solutions1995-04-012017-06-20Us
PyrazinamideTablet500 mg/1OralA S Medication Solutions1995-04-01Not applicableUs
PyrazinamideTablet500 mg/1OralRemedy Repack2013-08-212017-01-13Us
PyrazinamideTablet500 mg/1OralClinical Solutions Wholsesale1971-06-032017-06-20Us
PyrazinamideTablet500 mg/1OralRemedy Repack2008-05-21Not applicableUs
PyrazinamideTablet500 mg/1OralDAVA Pharmaceuticals, Inc.1971-06-03Not applicableUs
PyrazinamideTablet500 mg/1OralRemedy Repack2011-06-302016-10-21Us
PyrazinamideTablet500 mg/1OralRemedy Repack2016-12-27Not applicableUs
PyrazinamideTablet500 mg/1OralA S Medication Solutions1971-06-03Not applicableUs
PyrazinamideTablet500 mg/1OralAmerincan Health Packaging2015-09-01Not applicableUs
International/Other Brands
Piraldina (Bracco) / Prazina (Armoxindo) / Pyrafat (Riemser) / Pyrazide (Sanofi-Aventis) / Tebrazid (Valeant) / Tisamid (Orion)
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RifaterPyrazinamide (300 mg/1) + Isoniazid (50 mg/1) + Rifampicin (120 mg/1)Tablet, sugar coatedOralRemedy Repack2010-09-152016-10-13Us
RifaterPyrazinamide (300 mg) + Isoniazid (50 mg) + Rifampicin (120 mg)TabletOralSanofi Aventis1995-12-312017-03-29Canada
RifaterPyrazinamide (300 mg/1) + Isoniazid (50 mg/1) + Rifampicin (120 mg/1)Tablet, sugar coatedOralSanofi Aventis1994-05-31Not applicableUs
Categories
UNII
2KNI5N06TI
CAS number
98-96-4
Weight
Average: 123.1127
Monoisotopic: 123.043261797
Chemical Formula
C5H5N3O
InChI Key
IPEHBUMCGVEMRF-UHFFFAOYSA-N
InChI
InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)
IUPAC Name
pyrazine-2-carboxamide
SMILES
NC(=O)C1=NC=CN=C1

Pharmacology

Indication

For the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents.

Structured Indications
Pharmacodynamics

Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only against Mycobacterium tuberculosis. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication.

Mechanism of action

Pyrazinamide diffuses into M. tuberculosis, where the enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted (PMID: 11914348). However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids (PMID: 17101678). This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I (PMID: 17485499).

It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection.

Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria (PMID: 21835980).

TargetActionsOrganism
AFatty acid synthetase I (FASI)
inhibitor
Mycobacterium tuberculosis
Absorption

Rapidly and well absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

~10% (bound to plasma proteins)

Metabolism

Hepatic.

Route of elimination

Approximately 70% of an oral dose is excreted in the urine, mainly by glomerular filtration within 24 hours

Half life

9-10 hours (normal conditions)

Clearance
Not Available
Toxicity

Side effects include liver injury, arthralgias, anorexia, nausea and vomiting, dysuria,malaise and fever, sideroblastic anemia, adverse effects on the blood clotting mechanism or vascular integrity, and hypersensitivity reactions such as urticaria, pruritis and skin rashes.

Affected organisms
  • Mycobacterium tuberculosis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Pyrazinamide can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe metabolism of Pyrazinamide can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Pyrazinamide can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Pyrazinamide can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Pyrazinamide can be decreased when combined with Atomoxetine.Approved
AzithromycinThe metabolism of Pyrazinamide can be decreased when combined with Azithromycin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Pyrazinamide.Investigational
BoceprevirThe metabolism of Pyrazinamide can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Pyrazinamide can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Pyrazinamide can be decreased when it is combined with Bosentan.Approved, Investigational
CaffeineThe metabolism of Pyrazinamide can be decreased when combined with Caffeine.Approved
CarbamazepineThe metabolism of Pyrazinamide can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Pyrazinamide can be increased when it is combined with Ceritinib.Approved
CitalopramThe metabolism of Pyrazinamide can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Pyrazinamide can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Pyrazinamide can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Pyrazinamide can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Pyrazinamide can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Pyrazinamide can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Pyrazinamide can be decreased when combined with Crizotinib.Approved
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Pyrazinamide.Approved, Investigational, Vet Approved
Cyproterone acetateThe serum concentration of Pyrazinamide can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Pyrazinamide can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Pyrazinamide can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Pyrazinamide can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Pyrazinamide can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Pyrazinamide can be decreased when combined with Delavirdine.Approved
DihydroergotamineThe metabolism of Pyrazinamide can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Pyrazinamide can be decreased when combined with Diltiazem.Approved
DosulepinThe metabolism of Pyrazinamide can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Pyrazinamide can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Pyrazinamide can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Pyrazinamide can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Pyrazinamide can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Pyrazinamide can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Pyrazinamide can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Pyrazinamide can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Pyrazinamide can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Pyrazinamide can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Pyrazinamide can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Pyrazinamide can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Pyrazinamide can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Pyrazinamide can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Pyrazinamide can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Pyrazinamide can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Pyrazinamide can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Pyrazinamide can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Pyrazinamide can be decreased when combined with Ketoconazole.Approved, Investigational
LidocaineThe metabolism of Pyrazinamide can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Pyrazinamide can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Pyrazinamide can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Pyrazinamide can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Pyrazinamide can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Pyrazinamide can be increased when combined with Lumacaftor.Approved
MexiletineThe metabolism of Pyrazinamide can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Pyrazinamide can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Pyrazinamide can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Pyrazinamide can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Pyrazinamide can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Pyrazinamide can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Pyrazinamide can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Pyrazinamide can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Pyrazinamide can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Pyrazinamide can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Pyrazinamide can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Pyrazinamide can be increased when it is combined with Palbociclib.Approved
Peginterferon alfa-2bThe serum concentration of Pyrazinamide can be increased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Pyrazinamide can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Pyrazinamide can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Pyrazinamide can be increased when combined with Phenytoin.Approved, Vet Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Pyrazinamide.Approved
PosaconazoleThe metabolism of Pyrazinamide can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Pyrazinamide can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Pyrazinamide can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Pyrazinamide can be increased when combined with Rifabutin.Approved
RifampicinPyrazinamide may increase the hepatotoxic activities of Rifampicin.Approved
RifapentineThe metabolism of Pyrazinamide can be increased when combined with Rifapentine.Approved
RopiniroleThe metabolism of Pyrazinamide can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe metabolism of Pyrazinamide can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Pyrazinamide can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Pyrazinamide can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Pyrazinamide can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Pyrazinamide can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Pyrazinamide can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Pyrazinamide can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Pyrazinamide can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Pyrazinamide can be decreased when combined with Telithromycin.Approved
Tenofovir disoproxilThe metabolism of Pyrazinamide can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Pyrazinamide can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Pyrazinamide can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Pyrazinamide can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Pyrazinamide can be decreased when it is combined with Tocilizumab.Approved
VemurafenibThe serum concentration of Pyrazinamide can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Pyrazinamide can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Pyrazinamide can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Pyrazinamide can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Pyrazinamide can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Pyrazinamide can be decreased when combined with Zucapsaicin.Approved
Food Interactions
  • Take without regard to meals.

References

General References
  1. Authors unspecified: Controlled trial of four thrice-weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Lancet. 1981 Jan 24;1(8213):171-4. [PubMed:6109855]
  2. Authors unspecified: Controlled clinical trial of 4 short-couse regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis. Tubercle. 1983 Sep;64(3):153-66. [PubMed:6356538]
  3. Authors unspecified: A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. British Thoracic Society. Br J Dis Chest. 1984 Oct;78(4):330-6. [PubMed:6386028]
  4. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D: Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003 Jun 1;167(11):1472-7. Epub 2003 Jan 31. [PubMed:12569078]
  5. Boshoff HI, Mizrahi V, Barry CE 3rd: Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J Bacteriol. 2002 Apr;184(8):2167-72. [PubMed:11914348]
  6. Zimhony O, Vilcheze C, Arai M, Welch JT, Jacobs WR Jr: Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother. 2007 Feb;51(2):752-4. Epub 2006 Nov 13. [PubMed:17101678]
  7. Ngo SC, Zimhony O, Chung WJ, Sayahi H, Jacobs WR Jr, Welch JT: Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs. Antimicrob Agents Chemother. 2007 Jul;51(7):2430-5. Epub 2007 May 7. [PubMed:17485499]
  8. Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, Wang H, Zhang W, Zhang Y: Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011 Sep 16;333(6049):1630-2. doi: 10.1126/science.1208813. Epub 2011 Aug 11. [PubMed:21835980]
External Links
Human Metabolome Database
HMDB14483
KEGG Drug
D00144
KEGG Compound
C01956
PubChem Compound
1046
PubChem Substance
46507478
ChemSpider
1017
ChEBI
45285
ChEMBL
CHEMBL614
Therapeutic Targets Database
DAP000660
PharmGKB
PA451182
HET
PZA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pyrazinamide
ATC Codes
J04AM06 — Rifampicin, pyrazinamide, ethambutol and isoniazidJ04AK01 — PyrazinamideJ04AM05 — Rifampicin, pyrazinamide and isoniazid
AHFS Codes
  • 08:16.04 — Antituberculosis Agents
PDB Entries
3r4x / 3r55 / 3tuw / 5fpd
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedOtherTuberculosis1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
1CompletedTreatmentTuberculosis2
1RecruitingTreatmentTuberculosis1
1TerminatedTreatmentDisseminated Neuroblastoma / Recurrent Neuroblastoma1
1, 2RecruitingTreatmentTuberculous Meningitis1
2Active Not RecruitingTreatmentTuberculosis1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
2CompletedTreatmentTuberculosis2
2CompletedTreatmentTuberculosis, Pulmonary5
2Not Yet RecruitingTreatmentDrug-resistant Tuberculosis / Drug-Resistant Tuberculosis, Extremely / Tuberculosis / Tuberculosis, MDR / Tuberculosis, Multidrug Resistant / Tuberculosis, Pulmonary1
2RecruitingPreventionBone destruction / Cancer, Breast1
2RecruitingTreatmentTuberculosis1
2RecruitingTreatmentTuberculosis, Multidrug Resistant1
2SuspendedTreatmentTuberculosis, Pulmonary1
2Unknown StatusTreatmentTuberculosis1
2WithdrawnTreatmentLiver Cancer / Metastatic Cancers1
2, 3RecruitingTreatmentExtensively-drug Resistant Tuberculosis / Tuberculosis / Tuberculosis, Multidrug Resistant1
2, 3RecruitingTreatmentTuberculosis, Pulmonary1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis, Pulmonary1
3Active Not RecruitingTreatmentTuberculosis, Pulmonary, Drug Sensitive / Tuberculosis, Pulmonary, Multi Drug-resistant1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections / Tuberculosis1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
3CompletedTreatmentTuberculosis2
3RecruitingTreatmentMDR-TB1
3RecruitingTreatmentTuberculosis1
3RecruitingTreatmentTuberculosis, Multidrug Resistant1
3TerminatedTreatmentMultiple System Atrophy (MSA)1
3Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
3WithdrawnTreatmentTuberculosis Multi Drug Resistant Active1
4Active Not RecruitingPreventionInfection, Human Immunodeficiency Virus I1
4CompletedTreatmentDrug Induced Hepatotoxicity / Tuberculosis1
4CompletedTreatmentObstructive Sleep Apnea Syndrome (OSAS)1
4RecruitingTreatmentAIDS With Tuberculosis1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4RecruitingTreatmentTuberculosis, Pulmonary1
4RecruitingTreatmentTuberculosis, Spinal1
4Unknown StatusTreatmentHepatitis / Tuberculosis, Pulmonary1
4Unknown StatusTreatmentReinfection Pulmonary Tuberculosis1
Not AvailableCompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
Not AvailableCompletedSupportive CareBody Weight Changes / Motor Activities / Tuberculosis, Pulmonary1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis3
Not AvailableCompletedTreatmentTuberculosis1
Not AvailableUnknown StatusNot AvailableTuberculosis, Pulmonary1

Pharmacoeconomics

Manufacturers
  • Dava pharmaceuticals inc
  • Mikart inc
Packagers
Dosage forms
FormRouteStrength
TabletOral500 mg
TabletOral500 mg/1
TabletOral
Tablet, sugar coatedOral
Prices
Unit descriptionCostUnit
Rifater tablet3.1USD tablet
Pyrazinamide 500 mg tablet1.26USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)192 °CPhysProp
water solubility1.5E+004 mg/L (at 25 °C)MERCK INDEX (1996)
logP-0.60HANSCH,C ET AL. (1995)
logS-0.91ADME Research, USCD
pKa-0.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility93.7 mg/mLALOGPS
logP-0.71ALOGPS
logP-1.2ChemAxon
logS-0.12ALOGPS
pKa (Strongest Acidic)13.06ChemAxon
pKa (Strongest Basic)-0.68ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area68.87 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity30.45 m3·mol-1ChemAxon
Polarizability11.13 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9813
Blood Brain Barrier+0.9745
Caco-2 permeable+0.7222
P-glycoprotein substrateNon-substrate0.8219
P-glycoprotein inhibitor INon-inhibitor0.9709
P-glycoprotein inhibitor IINon-inhibitor0.9971
Renal organic cation transporterNon-inhibitor0.8985
CYP450 2C9 substrateNon-substrate0.8861
CYP450 2D6 substrateNon-substrate0.876
CYP450 3A4 substrateNon-substrate0.7754
CYP450 1A2 substrateNon-inhibitor0.8791
CYP450 2C9 inhibitorNon-inhibitor0.9545
CYP450 2D6 inhibitorNon-inhibitor0.9731
CYP450 2C19 inhibitorNon-inhibitor0.9547
CYP450 3A4 inhibitorNon-inhibitor0.9697
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9353
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9321
BiodegradationNot ready biodegradable0.9602
Rat acute toxicity1.8145 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9939
hERG inhibition (predictor II)Non-inhibitor0.9617
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.68 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0ab9-1900000000-d29284f74cafc89d62ad
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-9200000000-f1f9853e24fa676ffa99
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001j-9000000000-7be5ab1fa895dc272521
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000t-9000000000-9c4235602fdfd2d2cdeb
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-3009000000-ab4d0160c375af6d52ee
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyrazines. These are compounds containing a pyrazine ring, which is a six-member aromatic heterocycle, that consists of two nitrogen atoms (at positions 1 and 4) and four carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrazines
Direct Parent
Pyrazines
Alternative Parents
Heteroaromatic compounds / Carboximidic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
Pyrazine / Heteroaromatic compound / Azacycle / Carboximidic acid derivative / Carboximidic acid / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Organooxygen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrazines, monocarboxylic acid amide (CHEBI:45285) / a carboxamide (PYRAZINAMIDE)

Targets

1. Fatty acid synthetase I (FASI)
Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
Yes
Actions
Inhibitor
References
  1. Zimhony O, Cox JS, Welch JT, Vilcheze C, Jacobs WR Jr: Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7. [PubMed:10973326]
  2. Ngo SC, Zimhony O, Chung WJ, Sayahi H, Jacobs WR Jr, Welch JT: Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs. Antimicrob Agents Chemother. 2007 Jul;51(7):2430-5. Epub 2007 May 7. [PubMed:17485499]
  3. Zimhony O, Vilcheze C, Arai M, Welch JT, Jacobs WR Jr: Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother. 2007 Feb;51(2):752-4. Epub 2006 Nov 13. [PubMed:17101678]
  4. Schroeder EK, de Souza N, Santos DS, Blanchard JS, Basso LA: Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis. Curr Pharm Biotechnol. 2002 Sep;3(3):197-225. [PubMed:12164478]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [PubMed:8216357]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
References
  1. Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. [PubMed:8216357]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33