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Identification
NameBifonazole
Accession NumberDB04794
TypeSmall Molecule
GroupsApproved
DescriptionBifonazole is an azole antifungal drug. [Wikipedia]
Structure
Thumb
Synonyms
(+-)-1-(p,alpha-Diphenylbenzyl)imidazole
(+-)1-([1,1'-Biphenyl]-4-ylphenylmethyl)-1H-imidazole
1-((4-Biphenylyl)phenylmethyl)-1H-imidazole
1-(alpha-(4-Biphenylyl)benzyl)imidazole
1-(p,alpha-Diphenylbenzyl)imidazole
Bay h 4502
Bifonazol
Bifonazolum
Mycospor
Trifonazole
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AmycorMerck
AzolmenMenarini
Bayclear PlusBayer
BifonolMayado Seiyaku
CanesporBayer
CanestenBayer
MycosporBayer
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIQYJ305Z91O
CAS number60628-96-8
WeightAverage: 310.3917
Monoisotopic: 310.146998586
Chemical FormulaC22H18N2
InChI KeyOCAPBUJLXMYKEJ-UHFFFAOYSA-N
InChI
InChI=1S/C22H18N2/c1-3-7-18(8-4-1)19-11-13-21(14-12-19)22(24-16-15-23-17-24)20-9-5-2-6-10-20/h1-17,22H
IUPAC Name
1-[phenyl(4-phenylphenyl)methyl]-1H-imidazole
SMILES
C1=CN(C=N1)C(C1=CC=CC=C1)C1=CC=C(C=C1)C1=CC=CC=C1
Pharmacology
IndicationUsed for the treatment of various topical fungal infections, including athlete's foot (tinea pedis).
Structured Indications Not Available
PharmacodynamicsBifonazole is a type of antifungal medicine known as an imidazole. It kills fungi and yeasts by interfering with their cell membranes.
Mechanism of actionBifonazole works by inhibiting the production of a substance called ergosterol, which is an essential component of fungal cell membranes.It acts to destabilize the fungal cyctochrome p450 51 enzyme (also known as Lanosterol 14-alpha demethylase). This is vital in the cell membrance structure of the fungus. Its inhibition leads to cell lysis. The disruption in production of ergosterol disrupts the cell membrane and causes holes to appear. The cell membranes of fungi are vital for their survival. They keep unwanted substances from entering the cells and stop the contents of the cells from leaking out. As bifonazole causes holes to appear in the cell membranes, essential constituents of the fungal cells can leak out. This kills the fungi.
TargetKindPharmacological actionActionsOrganismUniProt ID
Lanosterol 14-alpha demethylaseProteinyes
inhibitor
YeastP10613 details
Cytochrome P450 2B6ProteinunknownNot AvailableHumanP20813 details
Related Articles
AbsorptionVery low absorption following topical administration (0.6% of an applied dose). In cases of skin lesions absorption is increased (2.5%).
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half life1-2 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Fungi
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AmlodipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Bifonazole.Approved, Investigational
AmrinoneThe risk or severity of adverse effects can be increased when Bifonazole is combined with Amrinone.Approved
AzelnidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Azelnidipine.Approved
AzimilideThe risk or severity of adverse effects can be increased when Bifonazole is combined with Azimilide.Investigational
BarnidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Barnidipine.Approved
BenidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Benidipine.Approved
BepridilThe risk or severity of adverse effects can be increased when Bifonazole is combined with Bepridil.Approved, Withdrawn
BuspironeThe metabolism of Buspirone can be decreased when combined with Bifonazole.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Bifonazole.Approved, Investigational
CaiThe risk or severity of adverse effects can be increased when Bifonazole is combined with Cai.Investigational
CilnidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Cilnidipine.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Bifonazole.Approved
CinnarizineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Cinnarizine.Approved
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Bifonazole.Approved, Investigational, Withdrawn
ClevidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Clevidipine.Approved
ConivaptanThe metabolism of Conivaptan can be decreased when combined with Bifonazole.Approved, Investigational
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Bifonazole.Approved, Investigational, Vet Approved
DarodipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Darodipine.Experimental
DidanosineDidanosine can cause a decrease in the absorption of Bifonazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Bifonazole is combined with Diltiazem.Approved
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Bifonazole.Approved, Investigational
DofetilideThe metabolism of Dofetilide can be decreased when combined with Bifonazole.Approved
DotarizineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Dotarizine.Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Efonidipine.Approved
EperisoneThe risk or severity of adverse effects can be increased when Bifonazole is combined with Eperisone.Approved, Investigational
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Bifonazole.Approved
FelodipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Felodipine.Approved, Investigational
FendilineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Fendiline.Withdrawn
FlunarizineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Flunarizine.Approved
FosphenytoinThe serum concentration of Bifonazole can be decreased when it is combined with Fosphenytoin.Approved
GabapentinThe risk or severity of adverse effects can be increased when Bifonazole is combined with Gabapentin.Approved, Investigational
GallopamilThe risk or severity of adverse effects can be increased when Bifonazole is combined with Gallopamil.Investigational
IsradipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Isradipine.Approved
LacidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Lacidipine.Approved
LamotrigineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Lamotrigine.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Lercanidipine.Approved, Investigational
LosartanThe metabolism of Losartan can be decreased when combined with Bifonazole.Approved
Magnesium SulfateThe risk or severity of adverse effects can be increased when Bifonazole is combined with Magnesium Sulfate.Approved, Vet Approved
ManidipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Manidipine.Approved
MibefradilThe risk or severity of adverse effects can be increased when Bifonazole is combined with Mibefradil.Withdrawn
NaftopidilThe risk or severity of adverse effects can be increased when Bifonazole is combined with Naftopidil.Investigational
NicardipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Nicardipine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Nifedipine.Approved
NiguldipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Niguldipine.Experimental
NiludipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Niludipine.Experimental
NilvadipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Nilvadipine.Approved
NimesulideThe risk or severity of adverse effects can be increased when Bifonazole is combined with Nimesulide.Approved, Withdrawn
NimodipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Nimodipine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Nisoldipine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Nitrendipine.Approved
PerhexilineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Perhexiline.Approved
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Bifonazole.Approved, Vet Approved
PimozideBifonazole may increase the arrhythmogenic activities of Pimozide.Approved
PinaveriumThe risk or severity of adverse effects can be increased when Bifonazole is combined with Pinaverium.Approved
PregabalinThe risk or severity of adverse effects can be increased when Bifonazole is combined with Pregabalin.Approved, Illicit, Investigational
PrenylamineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Prenylamine.Withdrawn
ProgesteroneThe therapeutic efficacy of Progesterone can be decreased when used in combination with Bifonazole.Approved, Vet Approved
QuinidineThe metabolism of Quinidine can be decreased when combined with Bifonazole.Approved
RanolazineThe metabolism of Ranolazine can be decreased when combined with Bifonazole.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Bifonazole.Approved
RifampicinThe serum concentration of Rifampicin can be increased when it is combined with Bifonazole.Approved
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Bifonazole.Approved
RisedronateThe risk or severity of adverse effects can be increased when Bifonazole is combined with Risedronate.Approved, Investigational
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Bifonazole.Approved
SucralfateSucralfate can cause a decrease in the absorption of Bifonazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Bifonazole.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Bifonazole.Approved, Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Bifonazole is combined with Tolfenamic Acid.Approved
TranilastThe risk or severity of adverse effects can be increased when Bifonazole is combined with Tranilast.Approved, Investigational
VerapamilThe risk or severity of adverse effects can be increased when Bifonazole is combined with Verapamil.Approved
VinpocetineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Vinpocetine.Investigational
XylometazolineThe risk or severity of adverse effects can be increased when Bifonazole is combined with Xylometazoline.Approved
ZiconotideThe risk or severity of adverse effects can be increased when Bifonazole is combined with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Bifonazole.Approved
Food InteractionsNot Available
References
Synthesis Reference

Regal, E., Draber, W., Buchel, K.H.and Plempel, M.; U.S. Patent 4,118,487; October 3,1978;
assigned to Bayer A.G.

US4118487
General References
  1. Watanabe S, Takahashi H, Nishikawa T, Takiuchi I, Higashi N, Nishimoto K, Kagawa S, Yamaguchi H, Ogawa H: A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis. Mycoses. 2006 May;49(3):236-41. [PubMed:16681817 ]
  2. Cho KJ, Su W, Chen WC, Law YP, Fang HC, Liu CP, Cheng JS, Lee KC, Lo YK, Chang HT, Huang JK, Jan CR: Mechanism of bifonazole-induced [Ca2+]i increases in MDCK renal tubular cells. Chin J Physiol. 2001 Sep 30;44(3):97-101. [PubMed:11767287 ]
  3. Tanuma H, Doi M, Sato N, Nishiyama S, Abe M, Kume H, Katsuoka K: Bifonazole (Mycospor cream) in the treatment of moccasin-type tinea pedis. Comparison between combination therapy of bifonazole cream + 10% urea ointment (Urepearl) and occlusive dressing therapy with the same agents. Mycoses. 2000;43(3-4):129-37. [PubMed:10907343 ]
  4. Berg D, Regel E, Harenberg HE, Plempel M: Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole. Arzneimittelforschung. 1984;34(2):139-46. [PubMed:6372801 ]
External Links
ATC CodesD01AC60D01AC10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9934
Blood Brain Barrier+0.9828
Caco-2 permeable+0.6357
P-glycoprotein substrateNon-substrate0.7794
P-glycoprotein inhibitor INon-inhibitor0.8037
P-glycoprotein inhibitor IINon-inhibitor0.8724
Renal organic cation transporterNon-inhibitor0.6194
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.7693
CYP450 1A2 substrateInhibitor0.7884
CYP450 2C9 inhibitorNon-inhibitor0.6395
CYP450 2D6 inhibitorInhibitor0.6381
CYP450 2C19 inhibitorInhibitor0.8503
CYP450 3A4 inhibitorInhibitor0.578
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9523
Ames testAMES toxic0.5674
CarcinogenicityNon-carcinogens0.9066
BiodegradationNot ready biodegradable0.9521
Rat acute toxicity2.3581 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.967
hERG inhibition (predictor II)Non-inhibitor0.6458
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point142Regal, E., Draber, W., Buchel, K.H.and Plempel, M.; U.S. Patent 4,118,487; October 3,1978; assigned to Bayer A.G.
logP4.77BIOBYTE (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.00245 mg/mLALOGPS
logP4.92ALOGPS
logP5.23ChemAxon
logS-5.1ALOGPS
pKa (Strongest Basic)6.69ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.82 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity97.94 m3·mol-1ChemAxon
Polarizability35.41 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Biphenyl
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
yes
Actions
inhibitor
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
Molecular Weight:
60674.965 Da
References
  1. Carrillo-Munoz AJ, Giusiano G, Ezkurra PA, Quindos G: Antifungal agents: mode of action in yeast cells. Rev Esp Quimioter. 2006 Jun;19(2):130-9. [PubMed:16964330 ]
  2. Rossello A, Bertini S, Lapucci A, Macchia M, Martinelli A, Rapposelli S, Herreros E, Macchia B: Synthesis, antifungal activity, and molecular modeling studies of new inverted oxime ethers of oxiconazole. J Med Chem. 2002 Oct 24;45(22):4903-12. [PubMed:12383016 ]
  3. Berg D, Plempel M: Bifonazole, a biochemist's view. Dermatologica. 1984;169 Suppl 1:3-9. [PubMed:6396116 ]
  4. Berg D, Regel E, Harenberg HE, Plempel M: Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole. Arzneimittelforschung. 1984;34(2):139-46. [PubMed:6372801 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
References
  1. 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 ]

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
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:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 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 or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
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 ]
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 ]
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Drug created on September 11, 2007 11:49 / Updated on August 17, 2016 12:24