General
Preferred name
PYRAZINAMIDE
Synonyms
Pyrazinamidum ()
Pyrazinecarboxamide ()
Pyrazinoic Acid Amide ()
Aldinamide ()
Pyrafat ()
Zinamide ()
Tebrazid ()
Aldinamid ()
NSC-14911 ()
MK-56 ()
Pyramizade ()
Pyrazine carboxylamide ()
Isopas ()
Novamid ()
Eprazin ()
Pyrazide ()
Farmizina ()
.alpha.-pyrazinamide ()
Unipyranamide ()
Pirazinamid ()
Rozide ()
Pirilene ()
Pirazimida ()
D-50 ()
P&D ID
PD001773
CAS
98-96-4
Tags
prodrug
natural product
drug
available
Approved by
FDA
First approval
1971
Drug Status
investigational
approved
Drug indication
Antibacterial (tuberculostatic)
Mycobacterium infection
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION This drug is often contained in fixed-mixture formulations with other antibacterial drugs beneficial in the treatment of tuberculosis (eg and ). (GtoPdb)
MOA Pyrazinamide diffuses into active _M. tuberculosis_ that express pyrazinamidase enzyme that converts pyrazinamide to the active form pyrazinoic acid. Pyrazinoic acid can leak out under acidic conditions to be converted to the protonated conjugate acid, which is readily diffused back into the bacilli and accumulate intracellularly. 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).
DESCRIPTION Antibiotic; tuberculostatic (LOPAC library)
Compound Sets
26
AdooQ Bioactive Compound Library
A10761
Cayman Chemical Bioactives
23416
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL614
ChEMBL Drugs
CHEMBL614
Drug Repurposing Hub
DrugBank
DB00339
DrugBank Approved Drugs
DB00339
DrugCentral
2328
DrugCentral Approved Drugs
2328
DrugMAP
DM4IF32
DrugMAP Approved Drugs
DM4IF32
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
7287
LOPAC library
MedChem Express Bioactive Compound Library
HY-B0271
NCATS Inxight Approved Drugs
2KNI5N06TI
NIH Clinical Collections (NCC)
NPC Screening Collection
Pandemic Response Box
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Pyrazinamide(Pyrazinoic-acid-amide)
TargetMol Bioactive Compound Library
T1426
The Spectrum Collection
External IDs
41
Properties
(calculated by RDKit )
Molecular Weight
123.04
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
1
Rotatable Bonds
1
Ring Count
1
Aromatic Ring Count
1
cLogP
-0.42
TPSA
68.87
Fraction CSP3
0.0
Chiral centers
0.0
Largest ring
6.0
QED
0.55
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
MOA
bacterial fatty acid synthase inhibitor
Fatty Acid Synthase inhibitor
Target
Fatty acid synthase
70S ribosome
FAS
FASN
antibiotic
Bacterial
Pathway
Metabolism
Anti-infection
Autophagy
Indication
tuberculosis
Therapeutic Class
Antitubercular Agents
Source data