Trimetrexate (CHEM002359)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (3)XML
Record Information
Version1.0
Creation Date2009-07-21 20:28:29 UTC
Update Date2026-05-14 16:58:18 UTC
Accession NumberCHEM002359
Identification
Common NameTrimetrexate
ClassSmall Molecule
DescriptionA nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. [PubChem]
Contaminant Sources
  • HMDB Contaminants - Urine
  • T3DB toxins
Contaminant Type
  • Amine
  • Antibiotic
  • Antifungal Agent
  • Antimetabolite, Antineoplastic
  • Antiprotozoal Agent
  • Drug
  • Ether
  • Folic Acid Antagonist
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
Trimetrexic acidGenerator
NeutrexinHMDB
TMQHMDB
TMXHMDB
Monohydrate, monoacetate trimetrexateHMDB
Trimetrexate ipsen brandHMDB
Trimetrexate monohydrate, monoacetateHMDB
JB 11HMDB
Hydrate, trimetrexateHMDB
Ipsen brand OF trimetrexateHMDB
JB-11HMDB
Trimetrexate hydrateHMDB
Chemical FormulaC19H23N5O3
Average Molecular Mass369.418 g/mol
Monoisotopic Mass369.180 g/mol
CAS Registry Number52128-35-5
IUPAC Name5-methyl-6-{[(3,4,5-trimethoxyphenyl)amino]methyl}quinazoline-2,4-diamine
Traditional Nametrimetrexate
SMILESCOC1=CC(NCC2=C(C)C3=C(C=C2)N=C(N)N=C3N)=CC(OC)=C1OC
InChI IdentifierInChI=1S/C19H23N5O3/c1-10-11(5-6-13-16(10)18(20)24-19(21)23-13)9-22-12-7-14(25-2)17(27-4)15(8-12)26-3/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24)
InChI KeyNOYPYLRCIDNJJB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazanaphthalenes
Sub ClassBenzodiazines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • Methoxyaniline
  • Aminophenyl ether
  • Aniline or substituted anilines
  • Phenylalkylamine
  • Phenoxy compound
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Secondary aliphatic/aromatic amine
  • Alkyl aryl ether
  • Aralkylamine
  • Aminopyrimidine
  • Pyrimidine
  • Benzenoid
  • Imidolactam
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Ether
  • Azacycle
  • Secondary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Amine
  • Primary amine
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point215-217°C
Boiling PointNot Available
Solubility31.4 mg/L
Predicted Properties
PropertyValueSource
Water Solubility0.031 g/LALOGPS
logP2.36ALOGPS
logP2.28ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)17.04ChemAxon
pKa (Strongest Basic)7.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area117.54 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity107.7 m³·mol⁻¹ChemAxon
Polarizability40.24 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ugj-0409000000-97a2080cda5a33464953Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dr-0409000000-a9fcda741827d39a85bcSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0903000000-d3e9f90709b809eb4f3dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-2911000000-97342eb0d2ab1fad8f13Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0209000000-e610f7928dd8d57d924cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0209000000-c28a10a57fcb7298832aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-9431000000-249d2de16520a2966585Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0109000000-a0632a23538eb5952dd1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0309000000-95e446c0693d174b1b3eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-0930000000-a03a19d017251496a0fbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009000000-f667390d4352ff65f24dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0gbi-0129000000-24c353e7a0c027954a2aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00vj-2493000000-41a8bf8d77660b776bdaSpectrum
Toxicity Profile
Route of ExposureIntravenous injection
Mechanism of ToxicityIn vitro studies have shown that trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of p.r.n. biosynthesis. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death.
MetabolismHepatic. Preclinical data strongly suggest that the major metabolic pathway is oxidative O-demethylation, followed by conjugation to either glucuronide or the sulfate. Route of Elimination: Ten to 30% of the administered dose is excreted unchanged in the urine. Half Life: 11 to 20 hours
Toxicity ValuesLD50: 62 mg/kg (Intravenous, Mouse) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use, with concurrent leucovorin administration (leucovorin protection), as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Also used to treat several types of cancer including colon cancer.
Minimum Risk LevelNot Available
Health EffectsAntibiotic resistance
SymptomsThe most common side effects from antibiotics are diarrhea, nausea, vomiting. Fungal infections of the mouth, digestive tract and vagina can also occur with antibiotics
TreatmentIn the event of overdose, Trimetrexate should be stopped and leucovorin should be administered at a dose of 40 mg/m2 every 6 hours for 3 days. (3)
Concentrations
Not Available
DrugBank IDDB01157
HMDB IDHMDB0015288
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkTrimetrexate
Chemspider ID5381
ChEBI ID119101
PubChem Compound ID5583
Kegg Compound IDC11154
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Martin Stogniew, Javad M. Zadei, “Compositions comprising trimetrexate and methods of their synthesis and use.” U.S. Patent US6258821, issued January, 1974.

MSDSNot Available
General ReferencesNot Available