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Fluconazole is a novel kind triazole drug of anti-fungal infection which was first successfully developed by the American Pfizer with broad-spectrum anti-fungal effect. It belongs to a kind of systemic anti-fungal products and has high selectivity on the inhibitory effect of the fungal cytochrome P450-dependent enzyme. It is also a kind of potent and specific inhibitor for the fungi alcohol synthesis. Clinically it is mainly used for the treatment of vaginal candidiasis, thrush, atrophic oral candidiasis, fungal meningitis, pulmonary fungal infections, abdominal infections, urinary tract infections and skin fungi infection. The main indication for fluconazole as follows: 1, systemic candidiasis: including candidemia, disseminated candidiasis and other forms of invasive Candida infections such as the peritoneum, endocardium, lungs and urinary tract infections. It can also be applied to patients of malignant tumors, special-care patients, patients who received radiotherapy, chemotherapy or immunosuppressive therapy as well as patients who are susceptible to other factors such as infection of Candida. It can also be used for prevention of the occurrence of candida infection for bone marrow transplant patients upon receiving cytotoxic drugs treatment or radiation treatment. 2, cryptococcosis: including cryptococcal meningitis and the cryptococcal infection in other parts (such as lung, skin). It can be applied to the patient of normal immune function, AIDS patients as well as patient of suppressed immune function due to organ transplant and other reasons. AIDS patients can administer this kind of drug for maintenance therapy and prevention of the relapse of cryptococcal disease. 3, mucosal candidiasis: including oropharyngeal, esophageal, non-invasive bronchial mucosal candidiasis, pulmonary candidiasis, Candida urine disease, mucocutaneous and chronic atrophic oral candidiasis. It can be applied to patients of both normal immune function and with impaired immune function. 4, fluconazole can be used as substitute of itraconazole for the treatment of blastomycosis and histoplasmosis. 5, it can be used for the treatment of acute or recurrent vaginal candidiasis. 6, for leukemia patients or patients of other malignant tumor who is susceptible to fungal infection upon undergoing chemotherapy or radiotherapy can apply it as means of preventive treatment. 7, it can be used for the treatment coccidioidomycosis. 8, it can be used for treatment of fungal skin disease including fungal skin infections such as body ringworm, tinea pedis, tinea versicolor, tinea capitis, onychomycosis and nail ringworm. 9, fluconazole can also be used for the treatment of skin chromomycosis. In August 2002, the voriconazole (Pfizer) which enters in the United States is the further structural modified derivative of fluconazole with its antibacterial activity against pathogenic yeast being higher than fluconazole. Some case reports have demonstrated that the drug can successfully cure some rare fungal disease. Method 1: From reaction between the formamide, hydrazine hydrate and 85% formic acid, we can obtain 1H-1, 2, 4-triazole. From phenylenediamine, we can obtain difluorobenzene, which is further subject to bromination to generate 2, 4-difluoro-bromobenzene. Magnesium was dissolved in anhydrous diethyl ether and added drop wise of the diethyl ether solution of 2, 4-difluoro-bromobenzene under ultrasonic irradiation, followed by adding drop wise of the diethyl ether solution of 1, 3-dichloroacetone under ice-cooling condition. Stir at room temperature overnight. Add glacial acetic acid and water. The separated organic layer was dried and concentrated. Concentrate, triazole, potassium carbonate and PEG600 were dissolved in anhydrous ethyl acetate and were subject to reflux. Then filter, wash with water to neutralization and dryness. The solvent was distilled off and was further subject to cyclohexane-ethyl acetate (1: 1) recrystallization to obtain the fluconazole with the overall yield being 33.6% and the m.p. being 138.5-140 ℃. The last step can also be carried out in propionitrile. 1, 3-dihalo (x = Br or Cl)-2-(2, 4-difluorophenyl)-2-propanol and 1H-1, 2, 4-triazol-propionitrile were put into propionitrile and subject to reflux under the catalysis of sodium hydroxide and PEG 600 phase transfer catalysis and obtain the fluconazole crude product. The crude product was dissolved in fatty alcohols (such as propanol, isopropanol or butanol, etc.), dissolved upon heating with a small amount of active carbon for decoloring and then cooled to give crystals which is the refined product of fluconazole with the melting point being 139~140 ℃. Method 2:2: 2, 4-difluorophenyl methyl is reacted with the Grignard reagent of 1-chloromethyl-1, 2, 4-triazole, and hydrolyzed to obtain fluconazole. Method 3: difluorophenyl is subject to bromination to generate 1-bromo-2, 4-difluorobenzene, and then further converted to Grignard reagent. The resulting Grignard reagent above is reacted with 1, 3-bis (1H-1, 2, 4-triazole group) acetone, followed by hydrolysis to give fluconazole. This product belongs to fluorinated triazole antifungal drug with the antifungal spectrum being similar as ketoconazole but antifungal activity being higher than ketoconazole. Its mechanism of action is through inhibition of essential component of the fungal cell membrane, the ergosterol biosynthesis enzyme, blocking the ergosterol synthesis and breaking the integrity of the fungal cell wall, further inhibiting their growth and reproduction. The product has potent antifungal activity against Candida albicans, Microsporum canis, Cryptococcus neoformans, histoplasma capsulatum and epidermophyton. Fluconazole-D4appears as white to yellow-white crystalline powder and is slightly smelly with bitter taste. It is easily soluble in glacial acetic acid, methanol or ethanol, hardly soluble in water and almost insoluble in ether with the melting point being 137~141.6 ℃, or melting point being 138~140 ℃ (derived from ethyl acetate-hexane). The above information is edited by the chemicalbook of Dai Xiongfeng. Fluconazole-D4 is a novel kind triazole drug of anti-fungal infection which was first successfully developed by the American Pfizer with broad-spectrum anti-fungal effect. It belongs to a kind of systemic anti-fungal products and has high selectivity on the inhibitory effect of the fungal cytochrome P450-dependent enzyme. It is also a kind of potent and specific inhibitor for the fungi alcohol synthesis. Clinically it is mainly used for the treatment of vaginal candidiasis, thrush, atrophic oral candidiasis, fungal meningitis, pulmonary fungal infections, abdominal infections, urinary tract infections and skin fungi infection. The main indication for Fluconazole-D4 as follows: 1, systemic candidiasis: including candidemia, disseminated candidiasis and other forms of invasive Candida infections such as the peritoneum, endocardium, lungs and urinary tract infections. It can also be applied to patients of malignant tumors, special-care patients, patients who received radiotherapy, chemotherapy or immunosuppressive therapy as well as patients who are susceptible to other factors such as infection of Candida. It can also be used for prevention of the occurrence of candida infection for bone marrow transplant patients upon receiving cytotoxic drugs treatment or radiation treatment. 2, cryptococcosis: including cryptococcal meningitis and the cryptococcal infection in other parts (such as lung, skin). It can be applied to the patient of normal immune function, AIDS patients as well as patient of suppressed immune function due to organ transplant and other reasons. AIDS patients can administer this kind of drug for maintenance therapy and prevention of the relapse of cryptococcal disease. 3, mucosal candidiasis: including oropharyngeal, esophageal, non-invasive bronchial mucosal candidiasis, pulmonary candidiasis, Candida urine disease, mucocutaneous and chronic atrophic oral candidiasis. It can be applied to patients of both normal immune function and with impaired immune function. 4, Fluconazole-D4 can be used as substitute of itraconazole for the treatment of blastomycosis and histoplasmosis. 5, it can be used for the treatment of acute or recurrent vaginal candidiasis. 6, for leukemia patients or patients of other malignant tumor who is susceptible to fungal infection upon undergoing chemotherapy or radiotherapy can apply it as means of preventive treatment. 7, it can be used for the treatment coccidioidomycosis. 8, it can be used for treatment of fungal skin disease including fungal skin infections such as body ringworm, tinea pedis, tinea versicolor, tinea capitis, onychomycosis and nail ringworm. 9, Fluconazole-D4 can also be used for the treatment of skin chromomycosis. In August 2002, the voriconazole (Pfizer) which enters in the United States is the further structural modified derivative of Fluconazole-D4 with its antibacterial activity against pathogenic yeast being higher than fluconazole. Some case reports have demonstrated that the drug can successfully cure some rare fungal disease. These are rare, but untoward reactions include nausea, abdominal discomfort, diarrhea and headache. Transient abnormalities of liver enzymes and rare serious skin reactions, including Stevens–Johnson syndrome, have been reported.Mucosal, cutaneous and systemic candidosis Coccidioidomycosis Cryptococcosis Dermatophytosis Pityriasis versicolorOral absorption: 93% Cmax 50 mg oral: c. 1 mg/L after 2 h Plasma half-life: 25–30 h Volume of distribution: 0.6–0.8 L/kg Plasma protein binding; 10% Absorption Oral absorption is rapid (1–3 h) and is not affected by food or intragastric pH. Blood concentrations increase in proportion to dosage. Maximum serum concentrations increase to about 2–3 mg/L after repeated dosing with 50 mg. Distribution It is widely distributed, achieving therapeutic concentrations in most tissues and body fluids. Concentrations in cerebrospinal fluid (CSF) are 50–60% of the simultaneous serum concentration in normal individuals and even higher in patients with meningitis. Metabolism and excretion More than 90% of an oral dose is eliminated in the urine: about 80% as unchanged drug and 10% as inactive metabolites. The drug is cleared by glomerular filtration, but there is significant tubular reabsorption. The plasma half-life is prolonged in renal failure, necessitating adjustment of the dosage.Fluconazole-D4 is removed during hemodialysis and, to a lesser extent, during peritoneal dialysis. In children the volume of distribution and plasma clearance are increased, and the half-life is considerably shorter (15–25 h). Triazole antifungal agent. Effective against Candida strains in vitro and in vivo .A synthetic bis(triazole) available for oral or parenteral administration. A prodrug formulation, fosfluconazole, is available for intravenous use in Japan.Resistant strains of C. albicans have been isolated from AIDS patients given long-term treatment for oral or esophageal candidosis. Strains of C. glabrata frequently become resistant during short courses of treatment. There are a few reports of fluconazole-resistant strains of Cryp. neoformans recovered from AIDS patients with relapsed meningitis. Most, but not all, C. albicans and C. glabrata strains resistant to fluconazole are cross-resistant to other azoles.Resistant strains of C. albicans have been isolated from AIDS patients given long-term treatment for oral or esophageal candidosis. Strains of C. glabrata frequently become resistant during short courses of treatment. There are a few reports of fluconazole-resistant strains of Cryp. neoformans recovered from AIDS patients with relapsed meningitis. Most, but not all, C. albicans and C. glabrata strains resistant to fluconazole are cross-resistant to other azoles.The spectrum is limited, but includes most Candida spp., Cryptococcus spp., dermatophytes and dimorphic fungi (Blast. dermatitidis, Coccidioides spp., Hist. capsulatum and Paracoccidioides brasiliensis). Strains of C. krusei appear to be insensitive.Resistant strains of C. albicans have been isolated from AIDS patients given long-term treatment for oral or esophageal candidosis. Strains of C. glabrata frequently become resistant during short courses of treatment. There are a few reports of fluconazole-resistant strains of Cryp. neoformans recovered from AIDS patients with relapsed meningitis. Most, but not all, C. albicans and C. glabrata strains resistant to fluconazole are cross-resistant to other azoles.Diflucan (Pfizer).Diflucan (Pfizer).A triazole broad-spectrum antifungal agent.Fluconazole-D4 is used for the treatment of fungal infections. anticholinergicLabelled Fluconazole (F421000). Used as an antifungal.Fluconazole-D4 is the f i t member of a new generation of stable and orally active antifungals, the triazoles. It is highly effective in the treatment of dermal and vaginal fungal infections; new indications currently under investigation include severe systemic mycoses such as disseminated candidiasis and cryptococcal meningitis in immunocompromised patients. Fluconazole-D4 is White to Off-White Solid Pfizer (United Kingdom)Labelled Fluconazole (F421000). Used as an antifungal.anticholinergicFluconazole-D4 is used for the treatment of fungal infections. A triazole broad-spectrum antifungal agent.Diflucan (Pfizer).The spectrum is limited, but includes most Candida spp., Cryptococcus spp., dermatophytes and dimorphic fungi (Blast. dermatitidis, Coccidioides spp., Hist. capsulatum and Paracoccidioides brasiliensis). Strains of C. krusei appear to be insensitive.Resistant strains of C. albicans have been isolated from AIDS patients given long-term treatment for oral or esophageal candidosis. Strains of C. glabrata frequently become resistant during short courses of treatment. There are a few reports of fluconazole-resistant strains of Cryp. neoformans recovered from AIDS patients with relapsed meningitis. Most, but not all, C. albicans and C. glabrata strains resistant to fluconazole are cross-resistant to other azoles.A synthetic bis(triazole) available for oral or parenteral administration. A prodrug formulation, fosfluconazole, is available for intravenous use in Japan.Triazole antifungal agent. Effective against Candida strains in vitro and in vivo .Oral absorption: 93% Cmax 50 mg oral: c. 1 mg/L after 2 h Plasma half-life: 25–30 h Volume of distribution: 0.6–0.8 L/kg Plasma protein binding; 10% Absorption Oral absorption is rapid (1–3 h) and is not affected by food or intragastric pH. Blood concentrations increase in proportion to dosage. Maximum serum concentrations increase to about 2–3 mg/L after repeated dosing with 50 mg. Distribution It is widely distributed, achieving therapeutic concentrations in most tissues and body fluids. Concentrations in cerebrospinal fluid (CSF) are 50–60% of the simultaneous serum concentration in normal individuals and even higher in patients with meningitis. Metabolism and excretion More than 90% of an oral dose is eliminated in the urine: about 80% as unchanged drug and 10% as inactive metabolites. The drug is cleared by glomerular filtration, but there is significant tubular reabsorption. The plasma half-life is prolonged in renal failure, necessitating adjustment of the dosage.Fluconazole-D4 is removed during hemodialysis and, to a lesser extent, during peritoneal dialysis. In children the volume of distribution and plasma clearance are increased, and the half-life is considerably shorter (15–25 h).