N1-Methyl-2-pyridone-5-carboxamide (CHEM003138)

Record Information
Version1.0
Creation Date2014-08-29 05:50:10 UTC
Update Date2026-08-24 08:42:56 UTC
Accession NumberCHEM003138
Identification
Common NameN1-Methyl-2-pyridone-5-carboxamide
ClassSmall Molecule
Description
N-methyl-2-pyridone-5-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. N-methyl-2-pyridone-5-carboxamide (2PY) is one of the end products of nicotinamide-adenine dinucleotide (NAD) degradation. Increased serum 2PY concentrations are observed in chronic renal failure (CRF) patients, which along with the deterioration of kidney function and its toxic properties (significant inhibition of PARP-1), suggests that 2PY is an uremic toxin. (2).
Contaminant Sources
  • FooDB Chemicals
  • HMDB Contaminants - Urine
  • T3DB toxins
Contaminant Type
  • Amide
  • Ester
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
MOLSDF3D SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
1-Methyl-5-carboxylamide-2-pyridoneChEBI
N'-methyl-2-pyridone-5-carboxamideChEBI
N(1)-Methyl-2-pyridone-5-carboxamideChEBI
N-Methyl-2-pyridone-5-carboxamideChEBI
N'Methyl-2-pyridone-5-carboxamideHMDB
Chemical FormulaC7H8N2O2
Average Molecular Mass152.151 g/mol
Monoisotopic Mass152.059 g/mol
CAS Registry Number701-44-0
IUPAC Name1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide
Traditional Name1-methyl-6-oxopyridine-3-carboxamide
SMILESCN1C=C(C=CC1=O)C(N)=O
InChI IdentifierInChI=1S/C7H8N2O2/c1-9-4-5(7(8)11)2-3-6(9)10/h2-4H,1H3,(H2,8,11)
InChI KeyJLQSXXWTCJPCBC-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
  • Dihydropyridinecarboxylic acid derivative
  • Nicotinamide
  • Dihydropyridine
  • Pyridinone
  • Hydropyridine
  • Heteroaromatic compound
  • Lactam
  • Carboximidic acid
  • Carboximidic acid derivative
  • Azacycle
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • 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 Solubility41.4 g/LALOGPS
logP-0.96ALOGPS
logP-1.1ChemAxon
logS-0.57ALOGPS
pKa (Strongest Acidic)15.93ChemAxon
pKa (Strongest Basic)1.36ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.4 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity40.76 m³·mol⁻¹ChemAxon
Polarizability14.71 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-2-pyridone-5-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 IDHMDB0004193
FooDB IDFDB023330
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN ID7025
PDB IDNot Available
Wikipedia LinkN1-Methyl-2-pyridone-5-carboxamide
Chemspider ID62899
ChEBI ID27410
PubChem Compound ID69698
Kegg Compound IDC05842
YMDB IDNot Available
ECMDB IDECMDB24086
References
Synthesis ReferenceGrudzinski, Stefan. Preparation of N-methyl-2-pyridone-5-carboxamide. Roczniki Chemii (1962), 36 1705-8.
MSDSNot Available
General References
1. Grudzinski, Stefan. Preparation of N-methyl-2-pyridone-5-carboxamide. Roczniki Chemii (1962), 36 1705-8.
2. Carter EG: Quantitation of urinary niacin metabolites by reversed-phase liquid chromatography. Am J Clin Nutr. 1982 Nov;36(5):926-30.
3. Patterson JI, Brown RR, Linkswiler H, Harper AE: Excretion of tryptophan-niacin metabolites by young men: effects of tryptophan, leucine, and vitamin B6 intakes. Am J Clin Nutr. 1980 Oct;33(10):2157-67.
4. 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.
5. 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.
6. Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043.
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=10694697
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=12694300
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=13211649
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=15663182
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=16029944
12. https://www.ncbi.nlm.nih.gov/pubmed/?term=17190852
13. https://www.ncbi.nlm.nih.gov/pubmed/?term=20073472
14. https://www.ncbi.nlm.nih.gov/pubmed/?term=20853461