Fluconazole

Base Information

• Chemical Name: Fluconazole
• CAS No.: 86386-73-4
• Deprecated CAS: 123631-92-5
• Molecular Formula: C13H12F2N6O
• Molecular Weight: 306.275
• Hs Code.: 29336990
• European Community (EC) Number: 627-806-0,691-089-0
• NSC Number: 758661
• UNII: 8VZV102JFY
• DSSTox Substance ID: DTXSID3020627
• Nikkaji Number: J23.677B
• Wikipedia: Fluconazole
• Wikidata: Q411478
• NCI Thesaurus Code: C500
• RXCUI: 4450
• Metabolomics Workbench ID: 42604
• ChEMBL ID: CHEMBL106
• Mol file: 86386-73-4.mol

Synonyms:Apo Fluconazole;Apo-Fluconazole;Béagyne;Diflucan;Fluc Hexal;Flucobeta;FlucoLich;Fluconazol AbZ;Fluconazol AL;Fluconazol Isis;Fluconazol ratiopharm;Fluconazol Stada;Fluconazol von ct;Fluconazol-Isis;Fluconazol-ratiopharm;Fluconazole;Flunazul;Fungata;Lavisa;Loitin;Neofomiral;Oxifungol;Solacap;Triflucan;UK 49858;UK-49858;UK49858;Zonal

Chemical Property of Fluconazole

Chemical Property:

• Appearance/Colour: white or off white crystalline powder
• Melting Point: 138-140 ºC
• Boiling Point: 579.8 ºC at 760 mmHg
• PKA: pKa 1.76±0.1(H2O t=24 I=0.1(NaCl)) (Uncertain)
• Flash Point: 304.4 ºC
• PSA: 81.65000
• Density: 1.49 g/cm³
• LogP: 0.73580
• Storage Temp.: −20°C
• Solubility.: DMSO: 5 mg/mL
• Water Solubility.: 1g/L(temperature not stated)
• XLogP3: 0.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 5
• Exact Mass: 306.10406535
• Heavy Atom Count: 22
• Complexity: 358

Purity/Quality:

99% ^*data from raw suppliers

Fluconazole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn,Xi,T,F
• Statements: 22-36/37/38-20/21/22-39/23/24/25-23/24/25-11
• Safety Statements: 26-36-36/37/39-24/25-45-36/37-16-7

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antifungal Agents
• Canonical SMILES: C1=CC(=C(C=C1F)F)C(CN2C=NC=N2)(CN3C=NC=N3)O
• Recent ClinicalTrials: The Effect of Medical Grade Honey Formulation (L-Mesitran) Administration on Recurrent Vulvovaginal Candidiasis Symptoms
• Recent EU Clinical Trials: Evaluation of the efficacy of treatment with mucosal bacterial vaccines (autovaccines) versus suppressive antibiotic treatment in subjects with hip or knee prosthesis infections.
• Recent NIPH Clinical Trials: Prospective Single-arm Trial of Fluconazole for Preventing Chemoradiation-associated Oral Mucositis in Head and Neck Cancer
• Uses: 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-D4 is used for the treatment of fungal infections. A triazole broad-spectrum antifungal agent.
• Production method: 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.
• Description: 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.
• Indications: Fluconazole (Diflucan) may be better absorbed and is possibly less hepatotoxic than ketoconazole, but it is considerably more expensive, an important consideration given the required length of therapy for most cutaneous fungal diseases.
• Therapeutic Function: Antifungal
• Clinical Use: Mucosal, cutaneous and systemic candidosis Coccidioidomycosis Cryptococcosis Dermatophytosis Pityriasis versicolor Fluconazole is very effective in the treatment of infections with most Candida spp. Thrush in the end-stage AIDS patient, often refractory to nystatin, clotrimazole, and ketoconazole, can usually be suppressed with oral fluconazole.AIDS patients with esophageal candidiasis also usually respond to fluconazole. Fluconazole may be an acceptable alternative to amphotericin B in the initial treatment of mild cryptococcal meningitis, and it has been shown to be superior to amphotericin B in the long-term prevention of relapsing meningitis (such patients require lifelong treatment.). Coccidioidal meningitis, previously treated with both intravenous and intrathecal amphotericin B, appears to respond at least as well to prolonged oral fluconazole therapy. Aspergillosis, mucormycosis, and pseudallescheriasis do not respond to fluconazole treatment. Sporotrichosis, histoplasmosis, and blastomycosis appear to be better treated with itraconazole, although fluconazole does appear to have significant activity against these dimorphic fungi.
• Drug interactions: Potentially hazardous interactions with other drugs Aminophylline: concentration of aminophylline possibly increased. Analgesics: increases concentration of celecoxib - halve celecoxib dose; concentration of flurbiprofen, ibuprofen and methadone increased; increases concentration of parecoxib - reduce parecoxib dose; inhibits metabolism of alfentanil; concentration of fentanyl possibly increased. Anti-arrhythmics: avoid concomitant use with amiodarone due to risk of QT prolongation. Antibacterials: avoid with erythromycin; increases rifabutin levels - reduce dose; metabolism accelerated by rifampicin; concentration of bedaquiline possibly increased - avoid if fluconazole for >14 days. Anticoagulants: potentiates effect of coumarins. Antidepressants: avoid concomitant use with reboxetine; concentration of amitriptyline and nortriptyline increased. Antidiabetics: possibly enhances hypoglycaemic effect of nateglinide; increases concentration of sulphonylureas. Antiepileptics: increases fosphenytoin and phenytoin levels; possibly increased carbamazepine concentration. Antimalarials: avoid concomitant administration with artemether/lumefantrine and piperaquine with artenimol. Antipsychotics: increased risk of ventricular arrhythmias with pimozide - avoid concomitant use; possibly increases lurasidone concentration; possibly increased quetiapine levels - reduce dose of quetiapine. Antivirals: increases nevirapine, ritonavir, tipranavir and zidovudine levels, and possibly saquinavir: concentration of simeprevir possibly increased - avoid. Anxiolytics and hypnotics: increases diazepam and midazolam levels. Avanafil: concentration of avanafil possibly increased. Bosentan: increased bosentan levels - avoid concomitant use. Ciclosporin: increases blood/serum ciclosporin levels. Clopidogrel: possibly reduced antiplatelet effect. Cytotoxics: possibly increased side effects of cyclophosphamide; concentration of bosutinib and possibly olaparib increased - avoid or reduce dose of bosutinib; possibly increases ibrutinib concentration - reduce ibrutinib dose; reduce dose of ruxolitinib. Dapoxetine: reduce dose of dapoxetine. Diuretics: increased eplerenone levels - avoid concomitant use; concentration of fluconazole increased by hydrochlorothiazide. Ergot alkaloids: increased risk of ergotism - avoid concomitant use. Guanfacine: possibly increased guanfacine dose - halve dose of guanfacine. Ivabradine: increased ivabradine levels - reduce initial dose. Ivacaftor: increased concentration of ivacaftor. Lipid-lowering drugs: possibly increased risk of myopathy with atorvastatin or simvastatin; concentration of fluvastatin increased possibly increased risk of myopathy; avoid with lomitapide. Retinoids: possibly increased risk of tretinoin toxicity. Sirolimus: may increase sirolimus concentration. Tacrolimus: increases blood/serum tacrolimus levels. Theophylline: possibly increases theophylline levels.

Technology Process of Fluconazole

There total 25 articles about Fluconazole which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.4%

anilazine (101-05-3) → fluconazole (86386-73-4)

Guidance literature:

With formic acid; sodium chloride; In dichloromethane; water;

Reference yield: 96.1%

1-chloro-2,4-difluorobenzene (1435-44-5) + 1,3-bis(1H-1,2,4-triazol-1-yl)propanone (98414-56-3) → fluconazole (86386-73-4)

Guidance literature:

1-chloro-2,4-difluorobenzene; With iodine; magnesium; lithium chloride; In 2-methyltetrahydrofuran; at 40 - 50 ℃; for 3h;

1,3-bis(1H-1,2,4-triazol-1-yl)propanone; In 2-methyltetrahydrofuran; at 20 - 40 ℃; for 2h;

Reference yield: 91.0%

1,3,5-Triazine (290-87-9) + 2-(2,4-difluorophenyl)-1-hydrazino-3-(1H-1,2,4-triazol-1-yl)propan-2-ol → fluconazole (86386-73-4)

Guidance literature:

With sodium hydroxide; formic acid; trifluoroacetic acid; In dichloromethane; water;

upstream raw materials:

1,2,4-Triazole

trimethylsulfoxonium iodide

1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone

1,3-(dichloro)-2-(2,4-difluorophenyl)propan-2-ol

Downstream raw materials:

FBr

FCl

[Zn(2-(2,4-difluorophenyl)-1,3-bis(1,2,4-triazol-1-yl)propan-2-ol)Cl₂(DMF)]2

Refernces

• 1、 Korwar, Sudha,Amir, Somi,Tosso, Perrer N.,Desai, Bimbisar K.,Kong, Caleb J.,Fadnis, Swara,Telang, Nakul S.,Ahmad, Saeed,Roper, Thomas D.,Gupton, B. Frank. "The Application of a Continuous Grignard Reaction in the Preparation of Fluconazole". . p. 6495 - 6498. Retrieved 2017.
• 2、 -. "Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof". . . Retrieved 2021/01/22.
• 3、 -. "A preparation method of fluconazole". Paragraph 0049-0051; 0065-0068. . Retrieved 2017/08/25.