Fluconazole antifungal agent

Fluconazole (4) (s the first member of a new generation of orally acti ve antifungal agents, highly effective in the treatment of dermal and vaginal infections [6, 7] S-Fluorocyrtosine (5) is also used to treat serious systemic fungal infections [5]... 

The Corey-Chaykovsky reaction incited some applications in medicinal chemistry. During the synthesis of analogs of fluconazole, an azole antifungal agent, treatment of 49 with 1 led to the corresponding epoxide, which was subsequently... 

This is not discussed in detail since mechanisms of resistance have been carefully reviewed (Ghannoum and Rice 1999). It was pointed out that resistance has not been associated with modification of the structure. For the 1,2,4-triazoles that have been widely used, their effect is due to inhibition of the synthesis of ergosterol that is the dominant component of fungal cell membranes. Resistance is generally associated with modification of the target enzymes, for example, the epoxidation of squalene (Terbinafine) or 14a-demethylase (Fluconazole). Resistance of Candida albicans to the azole antifungal agent fluconazole demonstrated, however, the simultaneous occurrence of several types of mechanism for resistance (Perea et al. 2001) ... 

Perea S, JL Lopez-Ribot, WR Kirkpatrick, RK McAtee, RA Santillan, M Martinez, D Calabrese, D Sanglard, TP Patterson (2001) Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antibicrob Agents Chemother 45 2676-2684. 

Pharmacology Fluconazole, a synthetic broad spectrum bis-triazole antifungal agent, is a highly selective inhibitor of fungal cytochrome P450 and sterol C-14 alpha-demethylation. 

Hypersensitivity to fluconazole or to any excipients in the product. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents use with caution in patients with hypersensitivity to other azoles. P.986... 

The importance of fluconazole as an antifungal agent has led to a renewed interest in triazole derivatives and a further exploration of methods of alkylation. Reaction of 4-amino triazole (27) with chloroacetophenones (28) gave the corresponding triazolium cations (29) which could be deaminated to (30) with nitrous acid (Scheme 4) <93JHC1405>. 

Therapy of fungal arthritis consists of amphotericin B in combination with surgical debridement. Azole antifungal agents including itraconazole, fluconazole, voriconazole, and posaconazole, are promising in the therapy of fungal arthritis. 

Ketoconazole remains useful in the treatment of cutaneous and mucous membrane dermatophyte and yeast infections, but it has been replaced by the newer triazoles in the treatment of most serious Candida infections and disseminated mycoses. Ketoconazole is usually effective in the treatment of thrush, but fluconazole is superior to ketoconazole for refractory thrush. Widespread dermatophyte infections on skin surfaces can be treated easily with oral ketoconazole when the use of topical antifungal agents would be impractical. Treatment of vulvovaginal candidiasis with topical imidazoles is less expensive. 

Azole derivatives currently available for oral treatment of systemic mycosis include fluconazole (Diflucan), itraconazole (Sporonax), and ketoconazole (Nizoral). As discussed in Chapter 48 Antifungal Agents, imidazole derivatives act by affecting the permeability of the cell membrane of... 

Itraconazole [it ra KON a zole] is a recent addition to the azole family of antifungal agents. Like fluconazole it is a synthetic triazole, and it also lacks the endocrinologic side effects of ketoconazole. Its mode of action is the same as that of the other azoles. Itraconazole is now the drug of choice for the treatment of blastomycosis. Unlike ketoconazole, it is effective in AIDS-associated histoplasmosis. However, current studies show that it may also be effective in the treatment of aspergillosis, candidemia, coccidioidomycosis, and cryptococcosis. Thus it has a broad antifungal spectrum. 

Robinson PA, Knirsch AK, Joseph JA. Fluconazole for life-threatening fungal infections in patients who cannot be treated with conventional antifungal agents. Rev Infect Dis I990 I2(Suppl 3) S349-63. 

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