Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
플루코나졸
플루코나졸 · Fluconazol · diflucan · FLUCONAZOLE-D4 · Fluconazole,2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol · 2,4-DIFLUORO-,1-BIS(1H-1,2,4-TRIAZOL-1-YLMETHYL)BENZYL ALCOHOL · 2-(2,4-difluorophenyl)-1,3-bis(1h-1,2,4-triazol-1-yl)propan-2-ol · luconazole
식별자 및 물리적 특성
| CAS No. | 86386-73-4 |
|---|---|
| 분자식 | C13H12F2N6O |
| 평균 분자량 | 306.27 g/mol |
| 단동위원소 질량 | 306.10406544 g/mol |
| SMILES | OC(Cn1cncn1)(Cn1cncn1)c1ccc(F)cc1F |
| InChIKey | RFHAOTPXVQNOHP-UHFFFAOYSA-N |
| PubChem CID | 3365 |
| ChEMBL | CHEMBL106 |
| ChEBI | CHEBI:46081 |
| EC No. | 627-806-0 |
| DTXSID | DTXSID3020627 |
| 현지명 | 플루코나졸 |
화학 및 물리적 성질
| XLogP | 0.4 |
|---|---|
| 극성 표면적 | 81.7 |
| 수소 결합 공여자 수 | 1 |
| 수소 결합 수용자 수 | 7 |
| 회전 가능 결합 수 | 5 |
| 무거운 원자 수 | 22 |
| 형식 전하 | 0 |
| 복잡도 | 358 |
| 물질 분류 | Pharmaceutical |
| 의약품 | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> AntibioticsPharmaceuticals -> Anti infectives for systemic use -> Antibacterials for systemic usePharmaceuticals -> Used in Switzerland |
| 농약 | Fungicides |
| LogP(분배 계수) | 0.40.63 |
| Color/Form | White crystalline powderCrystals from ethyl acetate/hexane |
| 용해도 | slightly soluble in waterPoorly soluble in water but can be dissolved in organic solvents such as chloroform, propylene glycol, and polyethoxylated castor oil (preparation for IV use but dangerous for dogs)Slightly soluble in water and saline1.39e+00 g/L34.9 [ug/mL] (The mean of the results at pH 7.4)DMSO: 5mg/mL 에 용해됨 |
| Human Drugs | Breast FeedingLactationMilk, HumanAntifungal AgentsFDA approved drugs -> Active ingredientAntifungal medicines |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| 녹는점 | 138-140 °C138 - 140 °C138-140°C |
| Physical Description | Solid |
| Dissociation Constants | 1.76pKa = 2.27 (1,2,4-triazole) |
| Collision Cross Section | 167.5 Ų [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: APCI+Dataset: TOXCASTSource Identifier: DTXSID3020627]156.2 Ų [M+H-H2O]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]163.9 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]163.4 Ų [M+H]+ [CCS Type: TW |
| 끓는 점 | 579.8±60.0 °C(Predicted) |
| 밀도 | 1.05 |
| 인화점 | 9℃ |
| 저장 조건 | 2-8°C |
| 물리적 상태 | 고체 |
| pKa(산도 계수) | pKa 1.76±0.1(H2O t=24 I=0.1(NaCl)) (Uncertain) |
| 색상 | 흰색에서 황백색까지 |
| 용해도 | 1g/L(온도 미표시) |
| Merck | 14,4122 |
| 헨리 상수 | 9.9×107 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 1,3 |
| InChI | InChI=1S/C13H12F2N6O/c14-10-1-2-11(12(15)3-10)13(22,4-20-8-16-6-18-20)5-21-9-17-7-19-21/h1-3,6-9,22H,4-5H2 |
| InChIKey | RFHAOTPXVQNOHP-UHFFFAOYSA-N |
| SMILES | C1(C=CC(F)=CC=1F)C(O)(CN1N=CN=C1)CN1N=CN=C1 |
화학적 성질
Fluconazole-D4 is White to Off-White Solid
안전 및 규제
| GHS 분류 | This chemical does not meet GHS hazard criteria for 0.5% (1 of 197) of reports.DangerH302 (99.5%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P263, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P308+P316, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 197 reports by companies from 33 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl fluconazole, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Hazard Classes and Categories | Acute Tox. 4 (99.5%) |
| 보관 조건 | Fluconazole tablets should be stored in tight containers at a temperature less than 30 °Cfluconazole powder for oral suspension should be stored at a temperature less than 30 °C. |
| 처리 방법 | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Treatment | In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted. (L1712) |
| 상호 작용 | Concurrent use of fluconazole and short-acting benzodiazepines, such as midazolam, may increase the concentration of the benzodiazepine and increase the psychomotor effectsconsider decreasing the benzodiazepine dose and monitor the patient carefully for signs of increased benzodiazepine exposure.Concurrent use of fluconazole and/or itraconazole with tolbutamide, chlorpropamide, glyburide, or glipizide has increased the plasma concentrations of these sulfonylurea agentshypoglycemia has been notedblood glucose concentrations should be monitored, and the dose of the oral hypoglycemic agent may need to be reduced.... In a small study, fluconazole was given with terfenadine and a small pharmacokinetic interaction was foundalthough no change in cardiac repolarization or accumulation of parent terfenadine was found, concurrent use of terfenadine with fluconazole at doses of 400 mg or greater per day is contraindicated.Concurrent use of cisapride with fluconazole ... is contraindicatedconcurrent use of this antifungal may inhibit the cytochrome P450 enzyme metabolic pathways, resulting in elevated plasma concentrations of cisapridethis has led to ventricular arrhythmias, including torsades de pointes and QT prolongation ...For more Interactions (Complete) data for FLUCONAZOLE (17 total), please visit the HSDB record page. |
| Hepatotoxicity | Transient mild-to-moderate elevations in serum aminotransferase levels occur in up to 5% of patients treated with fluconazole, but these abnormalities are usually asymptomatic and resolve even with continuation of the medication. ALT elevations above 8 times the upper limit of normal are reported to occur in 1% of patients taking fluconazole and to represent the most common adverse event leading to early discontinuation of treatment. Clinically apparent hepatotoxicity due to fluconazole is rare, but well described. The liver injury is typically hepatocellular, arises within the first few weeks of therapy and can be accompanied by signs of hypersensitivity such as fever, rash and eosinophilia. Fatal instances of fluconazole induced liver injury have been reported (Case 1), but most cases are self-limited, although recovery may be delayed for several weeks after stopping fluconazole and may be slow requiring 2 to 3 months. |
| 환경 거동 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5.3X10+4(SRC), determined from a structure estimation method(2), indicates that fluconazole is expected to be immobile in soil(SRC). Volatilization of fluconazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.0X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Fluconazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-9 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5.3X10+4(SRC), determined from a structure estimation method(2), indicates that fluconazole is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.0X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from an estimated log Kow of 0.25(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fluconazole, which has an estimated vapor pressure of 3.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase fluconazole may be removed from the air by wet and dry deposition(SRC). Fluconazole does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| 유해 작용 | Although most patients tolerate fluconazole, gastrointestinal symptoms are a frequently reported adverse event. These can include but are not limited to, nausea, abdominal pain, vomiting, and diarrhea, especially in children. |
| 노출 경로 | Intravenous, Oral |
| Milk Concentrations | EXPERIMENTAL: Fluconazole is distributed into human milk at concentrations similar to those achieved in plasma. Administration of a single 150-mg oral dose to several nursing women resulted in peak plasma fluconazole concentrations of 2.61 ug/mL (range: 1.57-3.65 ug/mL). |
| 독성 요약 | In a case report, acute toxicity of fluconazole has been described with peripheral nervous system involvement. In addition, the patient developed polyneuropathy, a confusional state, acute kidney injury, and thrombotic thrombocytopenic purpura.Fluconazole interacts with 14-&alphademethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Fluconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis. |
| Signs and Symptoms | Symptoms of overdose include hallucinations and paranoid behavior. |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of fluconazole can be estimated to be 5.3X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that fluconazole is expected to be immobile in soil. |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Signs and symptoms of overdose may include hallucinations, paranoid behaviors, decreased motility and respiration, ptosis, urinary incontinence, and cyanosis./CASE REPORTS/ While results of several studies evaluating pregnancy outcomes did not indicate an increased risk for congenital malformations in infants born to women who received fluconazole during pregnancy, data from these studies indicate that there has been at least one case each of congenital dislocation of the hip, lacrimal stenosis, partial syndactyly, ventricular septum deficiency, polydactyly or syndactyly, heart defect, or spina bifida in infants born to women who received the drug during pregnancy. In addition, there have been at least 3 reports of congenital abnormalities (craniofacial, skeletal, cardiac) in infants born to women who received fluconazole (400-800 mg daily) for the treatment of coccidioidomycosis during the first trimester./CASE REPORTS/ Hallucinations and paranoid behavior developed in a patient with human immunodeficiency virus (HIV) infection who reportedly ingested 8.2 g of fluconazole. The patient was hospitalized, and these manifestations resolved within 48 hours. |
| Artificial Pollution Sources | Fluconazole's production and use as an antifungal agent(1) may result in its release to the environment through various waste streams(SRC). |
| 수질 위해 등급(WGK) | 3 |
| RTECS 번호 | XZ4810000 |
| 운송 번호(UN) | UN1230 - class 3 - PG 2 - Methanol, solution |
| 관세 코드 | 29336990 |
| 위험 문구(R) | 22-36/37/38-20/21/22-39/23/24/25-23/24/25-11 |
| 위험 표시 | Xn,Xi,T,F |
| 안전 문구(S) | 26-36-36/37/39-24/25-45-36/37-16-7 |
| 위험 등급 | Acute Tox. 4 OralAquatic Chronic 3Lact.Repr. 1B |
| 저장 분류 | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| 유해 물질 데이터 | 86386-73-4(Hazardous Substances Data) |
용도
개요
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.
용도
Labelled Fluconazole (F421000). Used as an antifungal.
일반 설명
Fluconazole is used to treat adult neutropenic patients with invasive candidiasis (IC).