Voriconazole, a derivative of fluconazole, is a second-generation triazole with improved antifungal activity against Aspergillus and Fusarium species, P. boydii, and fluconazole-resistant Candida species. Voriconazole Pfizer development began under the original designation UK-109496, prior to its eventual approval as Vfend. The Voriconazole structure consists of a difluorophenyl group, a fluoropyrimidine ring, and a triazole moiety joined through a butanol backbone, with two defined stereocenters that determine its biological activity.
Application of Voriconazole
Pfizer Voriconazole programs secured approval for systemic prophylaxis and treatment of invasive fungal infections in adults and children, particularly those with hematological disorders or immunosuppressive therapy, where Aspergillus and resistant Candida infections carry substantial morbidity. The Voriconazole molecular formula and pharmacokinetic profile have made it a frequent reference compound in comparative antifungal studies, especially when contrasting a short-tailed triazole against longer-tailed agents like itraconazole.
In Vitro
Voriconazole inhibits 14α-lanosterol demethylase with an IC50 value of 53 nM, the fungal enzyme responsible for converting lanosterol into ergosterol, a sterol essential to fungal membrane structure. Molecular dynamics studies comparing four clinical triazoles found that long-tailed inhibitors such as posaconazole and itraconazole bind CYP51 more strongly than short-tailed inhibitors like fluconazole and voriconazole, since the longer tails form more extensive hydrophobic contacts within the binding cavity. 137234-62-9 reference standards are used across these assays for batch-to-batch consistency.
In Vivo
Following oral administration, voriconazole is rapidly and almost completely absorbed, with a high bioavailability of 96%. Beyond its antifungal use, it also inhibits brassinosteroid-dependent sterol biosynthesis in plants by blocking the same CYP51 enzyme, a finding that underscores how conserved this target is across kingdoms.
Biochemical and Physiological Actions
Voriconazole inhibits cytochrome P450-dependent 14α-lanosterol demethylation, acting against virtually all Candida species along with many Aspergillus species and other yeasts. The compound undergoes extensive hepatic metabolism via cytochrome P450 enzymes, primarily CYP2C9 and CYP3A4. The Voriconazole chemical structure incorporates a triazole-1-yl group that coordinates the heme iron of CYP51; a Voriconazole chemical structure diagram typically highlights this coordination site directly. CAS 137234-62-9 remains the identifier used across pharmacopeial and regulatory documentation.
Features and Benefits of Voriconazole
The Voriconazole molecular weight and short-tailed triazole architecture give it a pharmacokinetic profile distinct from longer-tailed azoles, including good central nervous system penetration that supports its use in cerebral fungal infections. Like fluconazole, it has high oral bioavailability and good cerebrospinal fluid penetration, but unlike fluconazole, it undergoes extensive hepatic metabolism and is highly protein bound. This profile, combined with its broad spectrum against resistant Candida and difficult molds, traces back to development work under the internal code PF-00579955 and keeps the compound a durable benchmark in antifungal pharmacology.
