Bifonazole

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	AU: S4 (Prescription only)/ Schedule 2;
Identifiers
	IUPAC name (RS)-1-[Phenyl(4-phenylphenyl)methyl]-1H-imidazole;
CAS Number	60628-96-8 ;
PubChem CID	2378 ;
DrugBank	DB04794 ;
ChemSpider	2287 ;
UNII	QYJ305Z91O ;
KEGG	D01775 ;
ChEBI	CHEBI:31286 ;
ChEMBL	ChEMBL277535 ;
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 ; Key:OCAPBUJLXMYKEJ-UHFFFAOYSA-N ;

Last updated September 07, 2025

Bifonazole (trade name Canespor among others^[2]) is an imidazole antifungal drug used in form of ointments.

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.^[4] Bifonazole is a potent aromatase inhibitor in vitro .^[5]^[6]

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.^[4]^[7]

Pharmacokinetics

Six hours after application, bifonazole concentrations range from 1000 μg/cm³ in the stratum corneum to 5 μg/cm³ in the papillary dermis.^[4]

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.^[8]^[9]^[10]

References

↑ "Therapeutic Goods (Poisons Standard— June 2025) Instrument 2025" (pdf). Therapeutic Goods Administration (TGA). May 2025. Retrieved 31 August 2025.
↑ International Drug Names : Bifonazole.
↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 502. ISBN 9783527607495.
1 2 3 Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Canesten Bifonazol-Creme.
↑ Trösken ER, Fischer K, Völkel W, Lutz WK (February 2006). "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". Toxicology. 219 (1–3): 33–40. Bibcode:2006Toxgy.219...33T. doi:10.1016/j.tox.2005.10.020. PMID 16330141.
↑ Egbuta C, Lo J, Ghosh D (December 2014). "Mechanism of inhibition of estrogen biosynthesis by azole fungicides". Endocrinology. 155 (12): 4622–4628. doi:10.1210/en.2014-1561. PMC 4239419 . PMID 25243857.
↑ Berg D, Regel E, Harenberg HE, Plempel M (1984). "Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole". Arzneimittel-Forschung. 34 (2): 139–146. PMID 6372801.
↑ US 4118487,Regel E, Draber W, Buchel KH, Plempel M,"Substituted azol-1-ylmethanes",issued 3 October 1978, assigned to Bayer Aktiengesellschaft
↑ Corelli F, Summa V, Brogi A, Monteagudo E, Botta M (1995). "Chiral Azole Derivatives. 2. Synthesis of Enantiomerically Pure 1-Alkylimidazoles". The Journal of Organic Chemistry. 60 (7): 2008–2015. doi:10.1021/jo00112a023.
↑ Hu Q, Negri M, Jahn-Hoffmann K, Zhuang Y, Olgen S, Bartels M, et al. (August 2008). "Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge". Bioorganic & Medicinal Chemistry. 16 (16): 7715–7727. doi:10.1016/j.bmc.2008.07.011. PMID 18674917.