Identification

Name
Econazole
Accession Number
DB01127  (APRD00943)
Type
Small Molecule
Groups
Approved
Description

A broad spectrum antimycotic with some action against Gram positive bacteria. It is used topically in dermatomycoses also orally and parenterally.

Structure
Thumb
Synonyms
  • (+-)-Econazole
  • 1-(2,4-Dichloro-beta-((P-chlorobenzyl)oxy)phenethyl)imidazole
  • Econazol
  • Econazole
  • Econazole Nitrate
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Econazole Nitrate CreamCream10 mg/1gTopicalAlvogen Inc.2017-09-07Not applicableUs
Econazole Nitrate CreamCream10 mg/1gTopicalLake Erie Medical Dba Quality Care Produts Llc2018-06-15Not applicableUs
Econazole Nitrate Topical Foam, 1%Aerosol, foam10 mg/1gTopicalXiromed Llc2016-12-092017-05-02Us
Ecostatin Cream 1%Cream1 %TopicalBristol Myers Squibb1982-12-312006-09-05Canada
Ecostatin Vaginal Ovule 150mgSuppository150 mgVaginalBristol Myers Squibb1979-12-312007-05-30Canada
EcozaAerosol, foam10 mg/1gTopicalExeltis Usa Dermatology, Llc2013-10-25Not applicableUs
SpectazoleCream10 mg/1gTopicalOrtho Mc Neil Pharmaceuticals1983-03-012006-07-01Us
SpectazoleCream10 mg/1gTopicalPhysicians Total Care, Inc.1982-12-232011-05-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Econazole NitrateCream10 mg/1gTopicalAidarex Pharmaceuticals LLC2002-11-26Not applicableUs
Econazole NitrateCream10 mg/1gTopicalPhysicians Total Care, Inc.2004-05-19Not applicableUs
Econazole NitrateCream10 mg/1gTopicalPerrigo New York Inc2006-08-08Not applicableUs
Econazole NitrateCream10 mg/1gTopicalPreferreed Pharmaceuticals Inc.2018-06-06Not applicableUs
Econazole NitrateCream10 mg/1gTopicalA-S Medication Solutions2006-08-082017-06-30Us
Econazole NitrateCream10 mg/1gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.2002-11-26Not applicableUs
Econazole NitrateCream10 mg/1gTopicalPrasco, Laboratories2007-09-012015-02-28Us
Econazole NitrateCream10 mg/1gTopicalPreferreed Pharmaceuticals Inc.2012-03-29Not applicableUs
Econazole NitrateCream10 mg/1gTopicalA-S Medication Solutions2002-11-262017-10-31Us
Econazole NitrateCream10 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2002-11-26Not applicableUs
International/Other Brands
Ecostatin (Bristol-Myers Squibb) / Gyno-Pevaryl (Janssen) / Ifenec (Italfarmaco) / Palavale (Otsuka Pharmaceutical) / Pevaryl (Janssen) / Spectazole (Healthcare)
Categories
UNII
6Z1Y2V4A7M
CAS number
27220-47-9
Weight
Average: 381.684
Monoisotopic: 380.024996233
Chemical Formula
C18H15Cl3N2O
InChI Key
LEZWWPYKPKIXLL-UHFFFAOYSA-N
InChI
InChI=1S/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
IUPAC Name
1-{2-[(4-chlorophenyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole
SMILES
ClC1=CC=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=C1

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Econazole is an antifungal medication related to fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox), and clotrimazole (Lotrimin, Mycelex). Econazole prevents fungal organisms from producing vital substances required for growth and function. This medication is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections.

Mechanism of action

Econazole 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.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
antagonist
Yeast
UNuclear receptor subfamily 1 group I member 2
partial agonist
Human
Absorption

After 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.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Overdosage of econazole in humans has not been reported to date. In mice, rats guinea pigs and dogs, the oral LD 50 values were found to be 462, 668, 272, and > 160 mg/kg, respectively.

Affected organisms
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference

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

US3717655
General References
Not Available
External Links
Human Metabolome Database
HMDB0015259
KEGG Drug
D03936
KEGG Compound
C08068
PubChem Compound
3198
PubChem Substance
46508881
ChemSpider
3086
BindingDB
31773
ChEBI
82873
ChEMBL
CHEMBL808
Therapeutic Targets Database
DAP001269
PharmGKB
PA164746010
IUPHAR
2446
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Econazole
ATC Codes
G01AF05 — EconazoleD01AC03 — EconazoleG01AF20 — Combinations of imidazole derivatives
FDA label
Download (203 KB)
MSDS
Download (72.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentInterdigital Tinea Pedis1
2CompletedTreatmentTinea Pedis1
2Unknown StatusTreatmentOnychomycosis1
3CompletedTreatmentTinea Pedis2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • DPT Laboratories Ltd.
  • E. Fougera and Co.
  • Medisca Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Perrigo Co.
  • Pharmedix
  • Physicians Total Care Inc.
  • Prasco Labs
  • Preferred Pharmaceuticals Inc.
  • Prescript Pharmaceuticals
  • Rebel Distributors Corp.
  • Taro Pharmaceuticals USA
Dosage forms
FormRouteStrength
CreamTopical10 mg/1
CreamTopical10 mg/1g
CreamTopical1 %
SuppositoryVaginal150 mg
Aerosol, foamTopical10 mg/1g
Prices
Unit descriptionCostUnit
Econazole Nitrate 1% Cream 85 gm Tube73.63USD tube
Econazole Nitrate 1% Cream 30 gm Tube32.16USD tube
Econazole Nitrate 1% Cream 15 gm Tube19.32USD tube
Econazole nitrate powder2.5USD g
Spectazole 1% cream1.33USD g
Econazole nitrate 1% cream0.93USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5993830No1998-01-162018-01-16Us
US10071054No2011-08-082031-08-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)162Godefroi, E.F. and Heeres, J.; U.S. Patent 3,717,655; February 20,1973; assigned to Jansen Pharmaceutica NV, Belgium.
logP5.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00148 mg/mLALOGPS
logP4.67ALOGPS
logP5.35ChemAxon
logS-5.4ALOGPS
pKa (Strongest Basic)6.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.05 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity98.26 m3·mol-1ChemAxon
Polarizability37.37 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9735
Blood Brain Barrier+0.9823
Caco-2 permeable+0.6096
P-glycoprotein substrateNon-substrate0.545
P-glycoprotein inhibitor INon-inhibitor0.7958
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterInhibitor0.6806
CYP450 2C9 substrateNon-substrate0.8407
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7017
CYP450 1A2 substrateInhibitor0.9472
CYP450 2C9 inhibitorInhibitor0.939
CYP450 2D6 inhibitorInhibitor0.9413
CYP450 2C19 inhibitorInhibitor0.9591
CYP450 3A4 inhibitorInhibitor0.8861
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9961
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.853
BiodegradationNot ready biodegradable0.9933
Rat acute toxicity2.8478 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Inhibitor0.8505
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0209000000-dd9a7887032ba981630f

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Dichlorobenzenes / N-substituted imidazoles / Aryl chlorides / Heteroaromatic compounds / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Benzylether / 1,3-dichlorobenzene / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / N-substituted imidazole / Imidazole / Azole / Heteroaromatic compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, ether, dichlorobenzene, monochlorobenzenes (CHEBI:82873)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Antagonist
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
ERG11
Uniprot ID
P10613
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
60674.965 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  2. Warrilow AG, Martel CM, Parker JE, Melo N, Lamb DC, Nes WD, Kelly DE, Kelly SL: Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51). Antimicrob Agents Chemother. 2010 Oct;54(10):4235-45. doi: 10.1128/AAC.00587-10. Epub 2010 Jul 12. [PubMed:20625155]
  3. Strushkevich N, Usanov SA, Park HW: Structural basis of human CYP51 inhibition by antifungal azoles. J Mol Biol. 2010 Apr 9;397(4):1067-78. doi: 10.1016/j.jmb.2010.01.075. Epub 2010 Feb 10. [PubMed:20149798]
  4. Jackson CJ, Lamb DC, Kelly DE, Kelly SL: Bactericidal and inhibitory effects of azole antifungal compounds on Mycobacterium smegmatis. FEMS Microbiol Lett. 2000 Nov 15;192(2):159-62. [PubMed:11064188]
  5. Pietila MP, Vohra PK, Sanyal B, Wengenack NL, Raghavakaimal S, Thomas CF Jr: Cloning and characterization of CYP51 from Mycobacterium avium. Am J Respir Cell Mol Biol. 2006 Aug;35(2):236-42. Epub 2006 Mar 16. [PubMed:16543605]
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Svecova L, Vrzal R, Burysek L, Anzenbacherova E, Cerveny L, Grim J, Trejtnar F, Kunes J, Pour M, Staud F, Anzenbacher P, Dvorak Z, Pavek P: Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48. Epub 2007 Nov 12. [PubMed:17998298]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  3. Tassaneeyakul W, Birkett DJ, Miners JO: Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica. 1998 Mar;28(3):293-301. [PubMed:9574817]
Details
3. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Monostory K, Hazai E, Vereczkey L: Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors. Chem Biol Interact. 2004 Apr 15;147(3):331-40. doi: 10.1016/j.cbi.2004.03.003. [PubMed:15135088]

Drug created on June 13, 2005 07:24 / Updated on November 03, 2018 15:31