BIFONAZOLE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C22H18N2
Molecular Weight	310.3917
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1=CN(C=N1)C(C2=CC=CC=C2)C3=CC=C(C=C3)C4=CC=CC=C4

InChI

InChIKey=OCAPBUJLXMYKEJ-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6396116 | https://www.ncbi.nlm.nih.gov/pubmed/2670516 | https://www.ncbi.nlm.nih.gov/pubmed/6372801

Bifonazole, a substituted imidazole, is a broad-spectrum antimycotic, interferes with sterol biosynthesis. Bifonazole possesses a sequential mode of action, namely inhibition of cytochrome P450-dependent C14-demethylation of sterols and direct inhibition of HMG-CoA-reductase. It possesses a broad spectrum of activity in vitro against dermatophytes, moulds, yeasts, dimorphic fungi and some Gram-positive bacteria. Bifonazole is an effective and well-tolerated treatment for superficial fungal infections of the skin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 19A1 39 Target ID: CHEMBL1978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25243857	Inhibitor 8504		270.0 nM [IC50]
Cytochrome P450 51 28 Target ID: CHEMBL1780 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2561184 \| https://www.ncbi.nlm.nih.gov/pubmed/6396116 \| https://www.ncbi.nlm.nih.gov/pubmed/6372801	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fungal skin infections 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6372801 https://www.ncbi.nlm.nih.gov/pubmed/2670516 https://www.ncbi.nlm.nih.gov/pubmed/6683530	Curative		Approved 8583	BIFONAZOLE Approved Use Bifonazole Cream is used to treat fungal skin infections such as ringworm, athlete’s foot and fungal sweat rash. The active substance in Canesten Bifonazole Cream is bifonazole. Bifonazole belongs to a group of medicines called imidazoles and is an antifungal agent which fights the cause of fungal skin infections.

C_max

Value	Dose	Co-administered	Analyte	Population
1 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/630004_2655708N1261_1_003_1F.pdf#page=22	15.2 mg single, transdermal dose: 15.2 mg route of administration: Transdermal experiment type: SINGLE co-administered:		BIFONAZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.4 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/630004_2655708N1261_1_003_1F.pdf#page=22	15.2 mg single, transdermal dose: 15.2 mg route of administration: Transdermal experiment type: SINGLE co-administered:		BIFONAZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 % 1 times / day multiple, topical Recommended Dose: 1 %, 1 times / day Route: topical Route: multiple Dose: 1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1458667/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1458667/	Sources: https://pubmed.ncbi.nlm.nih.gov/1458667/

PubMed

Title	Date	PubMed
Seborrhoeic dermatitis.	2010-12-07	21418692
Small scale screening to determine the ability of different polymers to inhibit drug crystallization upon rapid solvent evaporation.	2010-08-02	20536263
Prevention and treatment of intertrigo in large skin folds of adults: a systematic review.	2010-07-13	20626853
A New Validated HPLC Method for the Simultaneous Determination of 2-phenoxyethanol, Methylparaben, Ethylparaben and Propylparaben in a Pharmaceutical Gel.	2010-07	21218050
(Biphenyl-4-yl)(phen-yl)methanone.	2010-03-27	21580736
Otomycosis: Diagnosis and treatment.	2010-03-04	20347664
Association of high-dose bifonazole administration during early pregnancy and severe limb reduction defects in the newborn.	2010-03	20014436
Efficacy of intrasinusal administration of bifonazole cream alone or in combination with enilconazole irrigation in canine sino-nasal aspergillosis: 17 cases.	2010-02	20436862
Sulfonamide-1,2,4-thiadiazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies.	2010-02	20118573
Susceptibility testing of amorolfine, bifonazole and ciclopiroxolamine against Trichophyton rubrum in an in vitro model of dermatophyte nail infection.	2009-11	19888808
Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.	2009-09-14	19750012
In vitro susceptibility of nondermatophyte molds isolated from onycomycosis to antifungal drugs.	2009-08	19622458
Crystal structures of cytochrome P450 2B4 in complex with the inhibitor 1-biphenyl-4-methyl-1H-imidazole: ligand-induced structural response through alpha-helical repositioning.	2009-06-09	19397311
Calcium fingerprints induced by calmodulin interactors in eukaryotic cells.	2009-06	19133300
[Muscle effects due to the association of simvastatin and bifonazole cream].	2009-04-21	19374035
[Usefulness of bifonazole for treatment of tinea pedis in the 20th year after approval].	2009-04	19673350
Determination of azole antifungal medicines using zero-order and derivative UV spectrophotometry.	2009-02-21	19226964
Fungal nail infections: diagnosis and management.	2009-02	19391293
Chemical composition of essential oils of Thymus and Mentha species and their antifungal activities.	2009-01-07	19136911
[Cutaneous infection caused by Alternaria alternata in an immunocompetent host].	2009-01	19334395
[Guidelines for diagnosis and treatment of mucocutaneous candidiasis].	2009	19942790
In vitro antifungal activities of luliconazole, a new topical imidazole.	2009	19115136
Antifungal activity of the essential oil of Thymus vulgaris L. and thymol on experimentally induced dermatomycoses.	2008-12	18651285
Identification and analysis of conserved sequence motifs in cytochrome P450 family 2. Functional and structural role of a motif 187RFDYKD192 in CYP2B enzymes.	2008-08-01	18495666
In vitro antifungal activity of sertaconazole nitrate against recent isolates of onychomycosis causative agents.	2008-08	18676237
1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies.	2008-07-10	18529046
Thermodynamic fidelity of the mammalian cytochrome P450 2B4 active site in binding substrates and inhibitors.	2008-03-14	18241887
Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies.	2008-02-01	18053730
In vivo methods for the assessment of topical drug bioavailability.	2008-01	17985216
Tinea nigra by Hortaea werneckii, a report of 22 cases from Mexico.	2008	19287529
Topical fenticonazole in dermatology and gynaecology: current role in therapy.	2008	18840006
Generalized tinea corporis due to Trichophyton rubrum in ichthyosis vulgaris.	2007-09	17714151
Enantioselective separation of azole compounds by EKC. Reversal of migration order of enantiomers with CD concentration.	2007-08	17607804
Seborrhoeic dermatitis.	2007-07-01	19454093
Decreased susceptibility to antifungals in respiratory-deficient Kluyveromyces lactis mutants.	2007	18298045
[Bilateral proximal cellulitis and onychomycosis in both big toes due to Fusarium solani].	2006-12	17388651
Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles.	2006-11-10	16989930
Investigation of the role of cytochrome P450 2B4 active site residues in substrate metabolism based on crystal structures of the ligand-bound enzyme.	2006-11-01	17027909
Enantiomeric resolution of bifonazole by supercritical fluid chromatography.	2006-07	16894781
In vitro antifungal activity of luliconazole against clinical isolates from patients with dermatomycoses.	2006-06	16826352
A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis.	2006-05	16681817
MgSlt2, a cellular integrity MAP kinase gene of the fungal wheat pathogen Mycosphaerella graminicola, is dispensable for penetration but essential for invasive growth.	2006-04	16610742
Simultaneous determination of bifonazole and tinctures of calendula flower in pharmaceutical creams by reversed-phase liquid chromatography.	2006-03-11	16526446
Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction.	2006-03-03	16373351
Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation.	2006-02-15	16330141
What defines the quality of patient care in tinea pedis?	2006-02	16441623
High-performance thin-layer chromatography determination of some antimycotic imidazole derivatives and preservatives in medicinal creams and a gel.	2006-01-03	16386007
Athlete's foot.	2005-12	16620478
Chemical avulsion with urea nail lacquer.	2002-12	19753735
In vitro comparative study of the fungistatic and fungicidal activity of sertaconazole and other antifungals against Candida albicans.	1992-05	1627188

Patents

Sample Use Guides

In Vivo Use Guide

Bifonazole 1% w/w Cream. The cream should be applied thinly and evenly to the affected areas once daily, preferably at night before going to bed, and rubbed in gently. Treatment should be continued for 2-3 weeks, depending on the type of infection.

Route of Administration: Transdermal

In Vitro Use Guide

Concentrations of less than or equal to 5 ug/ml bifonazole have a fungicidal effect on dermatophytes, and a MIC value of less than or equal to 0.25 ug/ml has a maximal effect on Torulopsis glabrata. In ng concentrations bifonazole is effective on proliferating dermatophytes and pseudomycelia of Candida albicans.

Name

Type

Language

BIFONAZOLE

Official Name

English

MYCOSPOR

Preferred Name

English

(±)-1-(P,.ALPHA.-DIPHENYLBENZYL)IMIDAZOLE

Common Name

English

BIFONAZOLE [MART.]

Common Name

English

bifonazole [INN]

Common Name

English

BIFONAZOLE [EP MONOGRAPH]

Common Name

English

Bifonazole [WHO-DD]

Common Name

English

BAY-H-4502

Code

English

1H-IMIDAZOLE, 1-((1,1'-BIPHENYL)-4-YLPHENYLMETHYL)-, (±)-

Systematic Name

English

BIFONAZOLE [JAN]

Common Name

English

NSC-758954

Code

English

BIFONAZOLE [MI]

Common Name

English

BIFONAZOLE [EP IMPURITY]

Common Name

English

BAY H 4502

Code

English

BIFONAZOLE [USAN]

Common Name

English

D01AC10

Code

English

1-((4-BIPHENYLYL)-PHENYLMETHYL)-1H-IMIDAZOLE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C514