Chemistry:Bifonazole
Bifonazole (trade name Canespor among others[1]) is an imidazole antifungal drug used in form of ointments.
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
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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]
References
- ↑ International Drug Names: Bifonazole.
- ↑ (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 502. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA502.
- ↑ 3.0 3.1 3.2 (in German) Austria-Codex. Vienna: Österreichischer Apothekerverlag. 2015. Canesten Bifonazol-Creme.
- ↑ "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. February 2006. doi:10.1016/j.tox.2005.10.020. PMID 16330141. Bibcode: 2006Toxgy.219...33T.
- ↑ "Mechanism of inhibition of estrogen biosynthesis by azole fungicides". Endocrinology 155 (12): 4622–4628. December 2014. doi:10.1210/en.2014-1561. PMID 25243857.
- ↑ "Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole". Arzneimittel-Forschung 34 (2): 139–146. 1984. PMID 6372801.
- ↑ Regel E, Draber W, Buchel KH, Plempel M, "Substituted azol-1-ylmethanes", US patent 4118487, issued 3 October 1978
- ↑ "Chiral Azole Derivatives. 2. Synthesis of Enantiomerically Pure 1-Alkylimidazoles". The Journal of Organic Chemistry 60 (7): 2008–2015. 1995. doi:10.1021/jo00112a023.
- ↑ "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. August 2008. doi:10.1016/j.bmc.2008.07.011. PMID 18674917.
Further reading
- "Bifonazole. A review of its antimicrobial activity and therapeutic use in superficial mycoses". Drugs 38 (2): 204–225. August 1989. doi:10.2165/00003495-198938020-00004. PMID 2670516.
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