Itraconazole (CHEM002521)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (8)XML
Record Information
Version1.0
Creation Date2009-07-30 17:58:59 UTC
Update Date2026-05-14 16:58:24 UTC
Accession NumberCHEM002521
Identification
Common NameItraconazole
ClassSmall Molecule
DescriptionItraconazole is only found in individuals that have used or taken this drug. It is one of the triazole antifungal agents that inhibits cytochrome P-450-dependent enzymes resulting in impairment of ergosterol synthesis. It has been used against histoplasmosis, blastomycosis, cryptococcal meningitis & aspergillosis. [PubChem]Itraconazole interacts with 14-alpha demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • 14-alpha Demethylase Inhibitor
  • Amine
  • Antifungal Agent
  • Antiprotozoal Agent
  • Drug
  • Ether
  • Human Neurotoxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
ItrizoleChEBI
OriconazoleChEBI
SporanoxChEBI
ITCHMDB
ITCZHMDB
ITZHMDB
OrungalHMDB
Itraconazole janssen brandHMDB
Janssen brand OF itraconazoleHMDB
Janssen cilag brand OF itraconazoleHMDB
Janssen-cilag brand OF itraconazoleHMDB
Chemical FormulaC35H38Cl2N8O4
Average Molecular Mass705.633 g/mol
Monoisotopic Mass704.239 g/mol
CAS Registry Number84625-61-6
IUPAC Name1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-1,2,4-triazol-1-yl)methyl]-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
Traditional Nameitraconazole
SMILESCCC(C)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OC[C@H]2CO[C@@](CN3C=NC=N3)(O2)C2=C(Cl)C=C(Cl)C=C2)C=C1
InChI IdentifierInChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1
InChI KeyVHVPQPYKVGDNFY-ZPGVKDDISA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylpiperazines. Phenylpiperazines are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentPhenylpiperazines
Alternative Parents
Substituents
  • Phenylpiperazine
  • N-arylpiperazine
  • Phenyltriazole
  • Phenyl-1,2,4-triazole
  • Aminophenyl ether
  • Phenol ether
  • Phenoxy compound
  • Tertiary aliphatic/aromatic amine
  • 1,3-dichlorobenzene
  • Dialkylarylamine
  • Aniline or substituted anilines
  • Halobenzene
  • Alkyl aryl ether
  • Ketal
  • Chlorobenzene
  • Aryl halide
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl chloride
  • Azole
  • 1,2,4-triazole
  • Triazole
  • Meta-dioxolane
  • Heteroaromatic compound
  • Tertiary amine
  • Ether
  • Azacycle
  • Oxacycle
  • Acetal
  • Organochloride
  • Organohalogen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point166.2°C
Boiling PointNot Available
SolubilityInsoluble
Predicted Properties
PropertyValueSource
Water Solubility0.0096 g/LALOGPS
logP5.48ALOGPS
logP7.31ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)3.92ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area100.79 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity200.4 m³·mol⁻¹ChemAxon
Polarizability74.7 ųChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00e9-6214197000-1ee5b13e7088e9cfe8f4Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0lz0-0594300000-f8fca354ab686af07f2dSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0lz0-0594300000-f8fca354ab686af07f2dSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0udi-0329000000-18fc35342fd0b509b439Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0112100900-c45b863fbc00a8c449b4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-2014019700-85126d2b5b6964cb167dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-4911034000-399215ad81f2268c5d61Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9132010000-ae7c2d5fe82a8f94b236Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-9013020100-071002be4024d571dbb9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-9011000000-14b98a8a8e8671d57c64Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00or-7094010000-5df5528d83df0744427aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-1000002900-92f9c0efb49798e3bcf6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ufr-2020019400-0234895cdc4dcdafd7adSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0uyl-5284109100-cbdacae0a2b5183f54c6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0000001900-c0509f1b5423bc42d985Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0000037900-6204ee9c5fe37a35c4f4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9040343100-71b0ddcafedcd83a768cSpectrum
Toxicity Profile
Route of ExposureThe absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.
Mechanism of ToxicityItraconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
MetabolismItraconazole is extensively metabolized by the liver into a large number of metabolites, including hydroxyitraconazole, the major metabolite. The main metabolic pathways are oxidative scission of the dioxolane ring, aliphatic oxidation at the 1-methylpropyl substituent, N-dealkylation of this 1-methylpropyl substituent, oxidative degradation of the piperazine ring and triazolone scission. Route of Elimination: Itraconazole is metabolized predominately by the cytochrome P450 3A4 isoenzyme system (CYP3A4) in the liver, resulting in the formation of several metabolites, including hydroxyitraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a dose. Half Life: 21 hours
Toxicity ValuesNo significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.
Lethal DoseNo significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg. (1)
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB01167
HMDB IDHMDB0015298
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkItraconazole
Chemspider ID49927
ChEBI ID6076
PubChem Compound ID55283
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Jong-Soo Woo, Hong-Gi Yi, “Antifungal oral composition containing itraconazole and process for preparing same.” U.S. Patent US6039981, issued May, 1998.

MSDSLink
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=11219548
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=11403818
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=11422002
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=15521894
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=19025521
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=20400651
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=25326091