Butoconazole

Identification

Name
Butoconazole
Accession Number
DB00639  (APRD00834)
Type
Small Molecule
Groups
Approved
Description

Butoconazole is an imidazole antifungal used in gynecology.

Structure
Thumb
Synonyms
  • Alant starch
  • Butoconazol
  • Butoconazole
  • Butoconazolum
  • Compositenstärke
  • Dahlin
  • Polyfructosanum
External IDs
RS 35887 / RS 35887-00-10-3
Product Ingredients
IngredientUNIICASInChI Key
Butoconazole nitrate4805237NP564872-77-1ZHPWRQIPPNZNML-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gynazole.1Cream2 %VaginalFerring Pharmaceuticals2004-04-202014-01-15Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gynazole 1Cream100 mg/5gVaginalPerrigo New York Inc.2015-04-29Not applicableUs
Gynazole 1Cream100 mg/5gVaginalAmag Pharmaceuticals Inc2012-12-272016-10-19Us
International/Other Brands
Femstat (Bayer) / Femstat 3 (Bayer) / Gynazol (Gedeon Richter) / Gynazole (OM) / Gynazole-1 (Ferring) / Gynofort (Gedeon Richter) / Gynomyk (Will) / Inulead (Fuji Yakuhin) / Mycelex-3 (Bayer) / Volusol (Farmindustria)
Categories
UNII
0Q771797PH
CAS number
64872-76-0
Weight
Average: 411.776
Monoisotopic: 410.017802365
Chemical Formula
C19H17Cl3N2S
InChI Key
SWLMUYACZKCSHZ-UHFFFAOYSA-N
InChI
InChI=1S/C19H17Cl3N2S/c20-15-7-4-14(5-8-15)6-9-16(12-24-11-10-23-13-24)25-19-17(21)2-1-3-18(19)22/h1-5,7-8,10-11,13,16H,6,9,12H2
IUPAC Name
1-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)sulfanyl]butyl]-1H-imidazole
SMILES
ClC1=CC=C(CCC(CN2C=CN=C2)SC2=C(Cl)C=CC=C2Cl)C=C1

Pharmacology

Indication

For the local treatment of vulvovaginal candidiasis (infections caused by Candida)

Structured Indications
Pharmacodynamics

Butoconazole is an imidazole derivative that has fungicidal activity in vitro against Candida spp. and has been demonstrated to be clinically effective against vaginal infections due to Candida albicans. Candida albicans has been identified as the predominant species responsible for vulvovaginal candidasis.

Mechanism of action

The exact mechanism of the antifungal action of butoconazole is unknown, however, it is presumed to function as other imidazole derivatives via inhibition of steroid synthesis. Imidazoles generally inhibit the conversion of lanosterol to ergosterol via the inhibition of the enzyme cytochrome P450 14α-demethylase, resulting in a change in fungal cell membrane lipid composition. This structural change alters cell permeability and, ultimately, results in the osmotic disruption or growth inhibition of the fungal cell.

TargetActionsOrganism
AErgosterol
other
Candida albicans
Absorption

Following vaginal administration of butoconazole nitrate vaginal cream, 2% to 3 women, 1.7% (range 1.3-2.2%) of the dose was absorbed on average.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Oral, rat: LD50 = >1720 mg/kg.

Affected organisms
  • Fungi, yeast and protozoans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmlodipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Butoconazole.Approved, Investigational
AmrinoneThe risk or severity of adverse effects can be increased when Butoconazole is combined with Amrinone.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Atorvastatin.Approved
AzelnidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Azelnidipine.Approved, Investigational
AzimilideThe risk or severity of adverse effects can be increased when Butoconazole is combined with Azimilide.Investigational
BarnidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Barnidipine.Approved
BencyclaneThe risk or severity of adverse effects can be increased when Butoconazole is combined with Bencyclane.Experimental
BenidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Benidipine.Approved, Investigational
BepridilThe risk or severity of adverse effects can be increased when Butoconazole is combined with Bepridil.Approved, Withdrawn
BuspironeThe metabolism of Buspirone can be decreased when combined with Butoconazole.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Butoconazole.Approved, Investigational
CarboxyamidotriazoleThe risk or severity of adverse effects can be increased when Butoconazole is combined with Carboxyamidotriazole.Investigational
CaroverineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Caroverine.Experimental
CerivastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Cerivastatin.Withdrawn
CilnidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Cilnidipine.Approved, Investigational
CinnarizineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Butoconazole.Approved, Investigational, Withdrawn
ClevidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Clevidipine.Approved
ConivaptanThe metabolism of Conivaptan can be decreased when combined with Butoconazole.Approved, Investigational
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Butoconazole.Approved, Investigational, Vet Approved
DarodipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Darodipine.Experimental
DidanosineDidanosine can cause a decrease in the absorption of Butoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Butoconazole is combined with Diltiazem.Approved
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Butoconazole.Approved, Investigational
DofetilideThe metabolism of Dofetilide can be decreased when combined with Butoconazole.Approved
DotarizineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Dotarizine.Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Efonidipine.Approved, Investigational
EperisoneThe risk or severity of adverse effects can be increased when Butoconazole is combined with Eperisone.Approved, Investigational
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Butoconazole.Approved
FelodipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Felodipine.Approved, Investigational
FendilineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Fendiline.Withdrawn
FlunarizineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Flunarizine.Approved
FluvastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Fluvastatin.Approved
FosphenytoinThe serum concentration of Butoconazole can be decreased when it is combined with Fosphenytoin.Approved
GabapentinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Gabapentin.Approved, Investigational
GallopamilThe risk or severity of adverse effects can be increased when Butoconazole is combined with Gallopamil.Investigational
IsradipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Isradipine.Approved
LacidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Lacidipine.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Lamotrigine.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Lercanidipine.Approved, Investigational
LidoflazineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Lidoflazine.Experimental
LosartanThe metabolism of Losartan can be decreased when combined with Butoconazole.Approved
LovastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Lovastatin.Approved, Investigational
Magnesium SulfateThe risk or severity of adverse effects can be increased when Butoconazole is combined with Magnesium Sulfate.Approved, Vet Approved
ManidipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Manidipine.Approved, Investigational
MevastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Mevastatin.Experimental
MibefradilThe risk or severity of adverse effects can be increased when Butoconazole is combined with Mibefradil.Investigational, Withdrawn
NaftopidilThe risk or severity of adverse effects can be increased when Butoconazole is combined with Naftopidil.Investigational
NicardipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Nicardipine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Nifedipine.Approved
NiguldipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Niguldipine.Experimental
NiludipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Niludipine.Experimental
NilvadipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Nilvadipine.Approved, Investigational
NimesulideThe risk or severity of adverse effects can be increased when Butoconazole is combined with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Nimodipine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Nisoldipine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Nitrendipine.Approved, Investigational
OtiloniumThe risk or severity of adverse effects can be increased when Butoconazole is combined with Otilonium.Experimental, Investigational
PerhexilineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Perhexiline.Approved, Investigational
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Butoconazole.Approved, Vet Approved
PimozideButoconazole may increase the arrhythmogenic activities of Pimozide.Approved
PinaveriumThe risk or severity of adverse effects can be increased when Butoconazole is combined with Pinaverium.Approved
PitavastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Pitavastatin.Approved
PravastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Pravastatin.Approved
PregabalinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Pregabalin.Approved, Illicit, Investigational
PrenylamineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Prenylamine.Withdrawn
ProgesteroneThe therapeutic efficacy of Progesterone can be decreased when used in combination with Butoconazole.Approved, Vet Approved
QuinidineThe metabolism of Quinidine can be decreased when combined with Butoconazole.Approved
RanolazineThe metabolism of Ranolazine can be decreased when combined with Butoconazole.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Butoconazole.Approved
RifampicinThe serum concentration of Rifampicin can be increased when it is combined with Butoconazole.Approved
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Butoconazole.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Butoconazole.Approved, Investigational
RisedronateThe risk or severity of adverse effects can be increased when Butoconazole is combined with Risedronate.Approved, Investigational
RosuvastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Rosuvastatin.Approved
SimvastatinThe risk or severity of adverse effects can be increased when Butoconazole is combined with Simvastatin.Approved
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Butoconazole.Approved
SucralfateSucralfate can cause a decrease in the absorption of Butoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Butoconazole.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Butoconazole.Approved, Investigational
TerodilineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Terodiline.Experimental
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Tetrahydropalmatine.Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Butoconazole is combined with Tolfenamic Acid.Approved
TranilastThe risk or severity of adverse effects can be increased when Butoconazole is combined with Tranilast.Approved, Investigational
UbidecarenoneThe risk or severity of adverse effects can be increased when Butoconazole is combined with Ubidecarenone.Approved, Investigational, Nutraceutical
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Butoconazole.Approved
VerapamilThe risk or severity of adverse effects can be increased when Butoconazole is combined with Verapamil.Approved
VinpocetineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Vinpocetine.Investigational
XylometazolineThe risk or severity of adverse effects can be increased when Butoconazole is combined with Xylometazoline.Approved
ZiconotideThe risk or severity of adverse effects can be increased when Butoconazole is combined with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Butoconazole.Approved
Food Interactions
Not Available

References

Synthesis Reference

Laszlo Czibula, Laszlo Dobay, Eva Werkne Papp, Judit Nagyne Bagdy, Ferenc Sebok, "High Purity Butoconazole Nitrate with Specified Particle Size and a Process for the Preparation Thereof." U.S. Patent US20080221190, issued September 11, 2008.

US20080221190
General References
Not Available
External Links
Human Metabolome Database
HMDB14777
KEGG Drug
D00880
KEGG Compound
C08065
PubChem Compound
47472
PubChem Substance
46508016
ChemSpider
43192
BindingDB
79206
ChEBI
3240
ChEMBL
CHEMBL1295
Therapeutic Targets Database
DAP001267
PharmGKB
PA164781353
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Butoconazole
ATC Codes
G01AF15 — ButoconazoleG01AF20 — Combinations of imidazole derivatives
FDA label
Download (4.11 MB)
MSDS
Download (81.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentVaginal Infections1
3CompletedTreatmentVaginal Inflammation / Vulvovaginitis1
Not AvailableCompletedTreatmentVulvovaginal Candidiasis1

Pharmacoeconomics

Manufacturers
  • Roche palo alto llc
  • Bayer healthcare llc
  • Kv pharmaceutical co
Packagers
Dosage forms
FormRouteStrength
CreamVaginal100 mg/5g
CreamVaginal2 %
Prices
Unit descriptionCostUnit
Gynazole-1 cream10.89USD g
Femstat 3 cream0.96USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5266329No1993-11-302010-11-30Us
US5993856No1997-11-172017-11-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)~159°C with decomposition (nitrate salt)Not Available
water solubilityNitrate salt: 0.26 mg/ml (practically insoluble)Not Available
logP6.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000818 mg/mLALOGPS
logP6.7ALOGPS
logP6.55ChemAxon
logS-5.7ALOGPS
pKa (Strongest Basic)6.78ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.82 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity108.99 m3·mol-1ChemAxon
Polarizability41.01 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9258
Blood Brain Barrier+0.9716
Caco-2 permeable+0.6035
P-glycoprotein substrateNon-substrate0.6398
P-glycoprotein inhibitor INon-inhibitor0.6239
P-glycoprotein inhibitor IIInhibitor0.6822
Renal organic cation transporterInhibitor0.7157
CYP450 2C9 substrateNon-substrate0.7714
CYP450 2D6 substrateNon-substrate0.8601
CYP450 3A4 substrateNon-substrate0.6941
CYP450 1A2 substrateInhibitor0.934
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.8365
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9896
Ames testNon AMES toxic0.7381
CarcinogenicityNon-carcinogens0.9223
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.0919 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.792
hERG inhibition (predictor II)Inhibitor0.8263
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylbutylamines. These are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylbutylamines
Direct Parent
Phenylbutylamines
Alternative Parents
Thiophenol ethers / Dichlorobenzenes / Alkylarylthioethers / N-substituted imidazoles / Aryl chlorides / Heteroaromatic compounds / Sulfenyl compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 2 more
Substituents
Phenylbutylamine / Aryl thioether / 1,3-dichlorobenzene / Thiophenol ether / Chlorobenzene / Alkylarylthioether / Halobenzene / Aryl chloride / Aryl halide / N-substituted imidazole
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
conazole antifungal drug, aryl sulfide, imidazoles, imidazole antifungal drug, dichlorobenzene, monochlorobenzenes (CHEBI:3240)

Targets

1. Ergosterol
Kind
Small molecule
Organism
Candida albicans
Pharmacological action
Yes
Actions
Other
References
  1. Pfaller MA, Riley J, Koerner T: Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans. Diagn Microbiol Infect Dis. 1990 Jan-Feb;13(1):31-5. [PubMed:2184984]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:19