Bifonazole

Bifonazole (trade name Canespor among others^[1]) is an imidazole antifungal drug used in form of ointments.

Bifonazole

Clinical data
Trade names	Canespor, many others
AHFS/Drugs.com	International Drug Names
Routes of administration	Topical
ATC code	D01AC10 (WHO)
Legal status
Legal status	In general: Over-the-counter (OTC)
Identifiers
IUPAC name (RS)-1-[Phenyl(4-phenylphenyl)methyl]-1H-imidazole
CAS Number	60628-96-8 Y
PubChem CID	2378
DrugBank	DB04794 Y
ChemSpider	2287 Y
UNII	QYJ305Z91O
KEGG	D01775 Y
ChEBI	CHEBI:31286 Y
ChEMBL	ChEMBL277535 Y
CompTox Dashboard (EPA)	DTXSID9045631
ECHA InfoCard	100.056.651
Chemical and physical data
Formula	C22H18N2
Molar mass	310.400 g·mol−1
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
SMILES n1ccn(c1)C(c3ccc(c2ccccc2)cc3)c4ccccc4
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 Y Key:OCAPBUJLXMYKEJ-UHFFFAOYSA-N Y

It was patented in 1974 and approved for medical use in 1983.^[2] There are also combinations with carbamide for the treatment of onychomycosis.

Adverse effects

The most common side effect is a burning sensation at the application site. Other reactions, such as itching, eczema or skin dryness, are rare.^[3] Bifonazole is a potent aromatase inhibitor in vitro.^[4][5]

Pharmacology

Mechanism of action

Bifonazole has a dual mode of action. It inhibits fungal ergosterol biosynthesis at two points, via transformation of 24-methylendihydrolanosterol to desmethylsterol, together with inhibition of HMG-CoA. This enables fungicidal properties against dermatophytes and distinguishes bifonazole from other antifungal drugs.^[3][6]

Pharmacokinetics

Six hours after application, bifonazole concentrations range from 1000 μg/cm³ in the stratum corneum to 5 μg/cm³ in the papillary dermis.^[3]

Synthesis

Friedel-Crafts acylation between biphenyl (1) and benzoyl chloride (2) gives 4-phenylbenzophenone (3). Reduction with sodium borohydride gives the alcohol (4). Halogenation by thionyl chloride gives (5). Amination with imidazole (6) completes the synthesis of bifonazole.^[7][8][9]