Econazole (T3D2992)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2009-07-21 20:28:25 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D2992
Identification
Common NameEconazole
ClassSmall Molecule
DescriptionEconazole is only found in individuals that have used or taken this drug. It is a broad spectrum antimycotic with some action against Gram positive bacteria. It is used topically in dermatomycoses also orally and parenterally. [PubChem] Econazole 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. Econazole 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.
Compound Type
  • Amine
  • Antifungal Agent
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(+-)-Econazole
1-(2,4-Dichloro-beta-((P-chlorobenzyl)oxy)phenethyl)imidazole
Econazole Nitrate
Ecostatin
ECOZA
Gyno-Pevaryl
Ifenec
Palavale
Pevaryl
Spectazole
Chemical FormulaC18H15Cl3N2O
Average Molecular Mass381.684 g/mol
Monoisotopic Mass380.025 g/mol
CAS Registry Number27220-47-9
IUPAC Name1-{2-[(4-chlorophenyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole
Traditional Nameeconazole
SMILESClC1=CC=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=C1
InChI IdentifierInChI=1/C18H15Cl3N2O/c19-14-3-1-13(2-4-14)11-24-18(10-23-8-7-22-12-23)16-6-5-15(20)9-17(16)21/h1-9,12,18H,10-11H2
InChI KeyInChIKey=LEZWWPYKPKIXLL-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzylethers
Direct ParentBenzylethers
Alternative Parents
Substituents
  • Benzylether
  • 1,3-dichlorobenzene
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • N-substituted imidazole
  • Imidazole
  • Azole
  • Heteroaromatic compound
  • Ether
  • Dialkyl ether
  • Organoheterocyclic compound
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point162°C
Boiling PointNot Available
Solubility1.48e-03 g/L
LogP5.5
Predicted Properties
PropertyValueSource
Water Solubility0.0015 g/LALOGPS
logP4.67ALOGPS
logP5.35ChemAxon
logS-5.4ALOGPS
pKa (Strongest Basic)6.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.05 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity98.26 m³·mol⁻¹ChemAxon
Polarizability37.37 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-9341000000-4ffb0473a31cea3f8c182017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001i-0209000000-dd9a7887032ba981630f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-004i-1900000000-28f4c0046949a5e27ab12021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-004i-0900000000-f00842704123db9b04652021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-004i-0903000000-6c5549ea79b88c593f2e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-001i-0009000000-0e20351a1183f50f888e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-004i-5900000000-bb76504dc81de5c3b5792021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-004i-0900000000-a667527ad6d687e254002021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0019000000-e4e35751739b91041ba82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00m0-5169000000-ef3cb4a26c4fda6ee25d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9310000000-88884e5d802b100711cd2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-1009000000-cef44f57a37b6b00c9692016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-9001000000-7c677fea699efb1a72f32016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014l-9310000000-1d15b5e04ae4eb7ad4142016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-2039000000-17f63aee73e32a9737192021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9551000000-33222b3a25a12499d2cb2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00lr-9000000000-cd84e8c432915c9cc8692021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-7996a613e7d9dea8ceba2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-1219000000-1878634d92d58865370e2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00or-6910000000-84c9b556f80d887646102021-10-11View Spectrum
Toxicity Profile
Route of ExposureAfter topical application to the skin of normal subjects, systemic absorption of econazole nitrate is extremely low. Although most of the applied drug remains on the skin surface, drug concentrations were found in the stratum corneum which, by far, exceeded the minimum inhibitory concentration for dermatophytes.
Mechanism of ToxicityEconazole 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. Econazole 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.
MetabolismHepatic.
Toxicity ValuesLD50: 462 mg/kg (Oral, Mouse) (1) LD50: 462 mg/kg (Oral, Rat) (1) LD50: 668 mg/kg (Oral, Guinea pig) (1) LD50: >160 mg/kg (Oral, Dog) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor topical application in the treatment of tinea pedis, tinea cruris, and tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, Microsporum audouini, Microsporum gypseum, and Epidermophyton floccosum, in the treatment of cutaneous candidiasis, and in the treatment of tinea versicolor.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01127
HMDB IDHMDB15259
PubChem Compound ID3198
ChEMBL IDCHEMBL808
ChemSpider ID3086
KEGG IDC08068
UniProt IDNot Available
OMIM ID
ChEBI ID4754
BioCyc IDNot Available
CTD IDNot Available
Stitch IDEconazole
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEconazole
References
Synthesis Reference

Godefroi, E.F. and Heeres, J.; U.S. Patent 3,717,655; February 20,1973; assigned to Jansen Pharmaceutica NV, Belgium.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Cytochrome P450 3A4
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.431 uMNot AvailableBindingDB 50134038
References
  1. Roy K, Pratim Roy P: Comparative chemometric modeling of cytochrome 3A4 inhibitory activity of structurally diverse compounds using stepwise MLR, FA-MLR, PLS, GFA, G/PLS and ANN techniques. Eur J Med Chem. 2009 Jul;44(7):2913-22. doi: 10.1016/j.ejmech.2008.12.004. Epub 2008 Dec 16. [19128860 ]
Target Details
2. Lanosterol 14-alpha demethylase
General Function:
Sterol 14-demethylase activity
Specific Function:
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name:
CYP51A1
Uniprot ID:
Q16850
Molecular Weight:
56805.26 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.05 uMNot AvailableBindingDB 50134038
References
  1. Ekins S, Mankowski DC, Hoover DJ, Lawton MP, Treadway JL, Harwood HJ Jr: Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors. Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28. [17194716 ]
Target Details
3. Malate dehydrogenase, cytoplasmic
General Function:
Nad binding
Specific Function:
Not Available
Gene Name:
MDH1
Uniprot ID:
P40925
Molecular Weight:
36425.795 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5025 uMNot AvailableBindingDB 50134038
References
  1. Seidler J, McGovern SL, Doman TN, Shoichet BK: Identification and prediction of promiscuous aggregating inhibitors among known drugs. J Med Chem. 2003 Oct 9;46(21):4477-86. [14521410 ]
Target Details
4. Steroid 17-alpha-hydroxylase/17,20 lyase
General Function:
Steroid 17-alpha-monooxygenase activity
Specific Function:
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.
Gene Name:
CYP17A1
Uniprot ID:
P05093
Molecular Weight:
57369.995 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.325 uMNot AvailableBindingDB 50134038
References
  1. Clement OO, Freeman CM, Hartmann RW, Handratta VD, Vasaitis TS, Brodie AM, Njar VC: Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy. J Med Chem. 2003 Jun 5;46(12):2345-51. [12773039 ]