N1-Methyl-4-pyridone-3-carboxamide (CHEM003139)

Record Information
Version1.0
Creation Date2014-08-29 05:50:17 UTC
Update Date2026-08-24 08:42:55 UTC
Accession NumberCHEM003139
Identification
Common NameN1-Methyl-4-pyridone-3-carboxamide
ClassSmall Molecule
Description
N-methyl-4-pyridone-3-carboxamide is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. N1-Methyl-4-pyridone-5-carboxamide (4PY ) is a normal human metabolite (one of the end products of nicotinamide-adenine dinucleotide (NAD) degradation). 4PY concentration in serum is elevated in non-dialyzed chronic renal failure (CRF) patients when compared with controls. (2).
Contaminant Sources
  • FooDB Chemicals
  • HMDB Contaminants - Urine
  • T3DB toxins
Contaminant Type
  • Amide
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
1,4-Dihydro-1-methyl-4-oxo-3-pyridinecarboxamideChEBI
1-Methyl-4-oxo-1,4-dihydro-3-pyridinecarboxamideChEBI
1-Methyl-4-pyridone-3-carboximideChEBI
1-Methyl-4-pyridone-5-carboxamideChEBI
3-(Aminocarbonyl)-1-methyl-4(1H)-pyridoneChEBI
5-Aminocarbonyl-1-methyl-4(1H)-pyridoneChEBI
N'-methyl-4-pyridone-5-carboxamideChEBI
N-Methyl-4-pyridone-5-carboxamideChEBI
N1-Methyl-4-pyridone-5-carboxamideChEBI
1-Methyl-4-pyridone-3-carboxamideHMDB
Chemical FormulaC7H8N2O2
Average Molecular Mass152.151 g/mol
Monoisotopic Mass152.059 g/mol
CAS Registry Number769-49-3
IUPAC Name1-methyl-4-oxo-1,4-dihydropyridine-3-carboxamide
Traditional Name1-methyl-4-oxopyridine-3-carboxamide
SMILESCN1C=CC(=O)C(=C1)C(N)=O
InChI IdentifierInChI=1S/C7H8N2O2/c1-9-3-2-6(10)5(4-9)7(8)11/h2-4H,1H3,(H2,8,11)
InChI KeyKTLRWTOPTKGYQY-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as nicotinamides. These are heterocyclic aromatic compounds containing a pyridine ring substituted at position 3 by a carboxamide group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassPyridinecarboxylic acids and derivatives
Direct ParentNicotinamides
Alternative Parents
Substituents
  • Nicotinamide
  • Dihydropyridine
  • Hydropyridine
  • Vinylogous amide
  • Heteroaromatic compound
  • Carboxamide group
  • Primary carboxylic acid amide
  • Cyclic ketone
  • Carboxylic acid derivative
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Nicotinate and Nicotinamide MetabolismSMP00048 map00760
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility115 g/LALOGPS
logP-1ALOGPS
logP-0.56ChemAxon
logS-0.12ALOGPS
pKa (Strongest Acidic)15.73ChemAxon
pKa (Strongest Basic)0.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.4 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity40.81 m³·mol⁻¹ChemAxon
Polarizability14.7 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as N-methyl-4-pyridone-3-carboxamide are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (3). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (4).
MetabolismUremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNaturally produced by the body (endogenous).
Minimum Risk LevelNot Available
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
SymptomsAs a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Concentrations
Not Available
External Links
DrugBank IDNot Available
HMDB IDHMDB0004194
FooDB IDFDB023331
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkNot Available
Chemspider ID389671
ChEBI ID27838
PubChem Compound ID440810
Kegg Compound IDC05843
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceChaykin, Sterling. Biosynthesis of N-methyl-4-pyridone-3-carboxamide. Biochimica et Biophysica Acta, General Subjects (1964), 82(3), 633-4.
MSDSNot Available
General References
1. Chaykin, Sterling. Biosynthesis of N-methyl-4-pyridone-3-carboxamide. Biochimica et Biophysica Acta, General Subjects (1964), 82(3), 633-4.
2. Rutkowski B, Slominska E, Szolkiewicz M, Smolenski RT, Striley C, Rutkowski P, Swierczynski J: N-methyl-2-pyridone-5-carboxamide: a novel uremic toxin? Kidney Int Suppl. 2003 May;(84):S19-21.
3. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24.
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=12694300
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=13692332
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=17190852