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Niclosamid
NICLOSAMID · 5-CHLORO-N-(2-CHLORO-4-NITROPHENYL)-2-HYDROXYBENZAMIDE · YOMESAN · niclocide · tredemine · bayluscid · NICLOSAMIDE (BAY2353) · mato
Identifikatoren & physikalische Daten
| CAS No. | 50-65-7 |
|---|---|
| Summenformel | C13H8Cl2N2O4 |
| Durchschnittliche Molmasse | 327,12 g/mol |
| Monoisotopische Masse | 325,9861121 g/mol |
| SMILES | O=C(Nc1ccc([N+](=O)[O-])cc1Cl)c1cc(Cl)ccc1O |
| InChIKey | RJMUSRYZPJIFPJ-UHFFFAOYSA-N |
| PubChem CID | 4477 |
| ChEMBL | CHEMBL1448 |
| ChEBI | CHEBI:7553 |
| EC No. | 200-056-8 |
| DTXSID | DTXSID7040362 |
| Lokaler Name | Niclosamid |
Chemische & physikalische Eigenschaften
| XLogP | 4 |
|---|---|
| Polarare Oberfläche (TPSA) | 95,2 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 2 |
| Schwere Atome | 21 |
| Formalladung | 0 |
| Komplexität | 404 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antibiotics |
| LogP (Verteilungskoeffizient) | log Kow = 10 @ pH 9.6 |
| Geschmack | Tasteless |
| Color/Form | PALE, YELLOW CRYSTALSALMOST COLORLESS CRYSTALSA cream-colored or yellowish-white powderBright yellow crystalline solid |
| Löslichkeit | SPARINGLY SOL IN CHLOROFORM, ETHER, ETHANOLSOL IN ACETONESol at 20 °C in 150 parts of alcoholIn water = 5-8 mg/L at 20 °CFor more Solubility (Complete) data for NICLOSAMIDE (8 total), please visit the HSDB record page.acetone: methanol: soluble50mg/mL (methanol:acetone (1:1))13.32mg/L(25 ºC) |
| Human Drugs | Breast FeedingLactationAnti-infective AgentsAntiparasitic AgentsAnthelminticsAnticestodal AgentsAntinematodal AgentsMolluscacidesFDA approved drugs -> Active ingredientIntestinal anthelminthics |
| Schmelzpunkt | 225-230 °C225-230° |
| Dampfdruck | <9.87X10-9 mm Hg at 20 °C |
| Physical Description | Solid |
| Stability/Shelf Life | TABLETS ARE SENSITIVE TO MOISTURE.Decomp more rapidly in the presence of ... UV irradiation.It is stable to heat and is hydrolysed by concentrated acid or alkali. |
| Collision Cross Section | 164.6 Ų [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID7040362]168.3 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Other Experimental Properties | Hydrolysed in aqueous solution with a decomposition half-life at 20 °C of 7 days (pH 6.9), 18.8 days (pH 13.3). Stable to heat. Decomposes under UV irradiation. Hydrolysed by concentrated acid or alkali.Decomposes at 208 °CIts biological effectiveness in water is stable at pH 5-9 and is also largely independent of the concentration of calcium and magnesium ions. |
| Siedepunkt | 424.5±45.0 °C(Predicted) |
| Dichte | 1.6646 (rough estimate) |
| Brechungsindex | 1.6200 (estimate) |
| Lagerbedingungen | Sealed in dry,Room Temperature |
| Aggregatzustand | Pale yellow solid |
| pKa (Säurekonstante) | 7.45±0.43(Predicted) |
| Farbe | Yellow |
| BRN | 2820605 |
| Henry-Konstante | 1.5×104 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 4 |
| Stabilität | Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. |
| Hauptanwendungen | pharmaceutical (small molecule) |
| InChI | 1S/C13H8Cl2N2O4/c14-7-1-4-12(18)9(5-7)13(19)16-11-3-2-8(17(20)21)6-10(11)15/h1-6,18H,(H,16,19) |
| InChIKey | RJMUSRYZPJIFPJ-UHFFFAOYSA-N |
| SMILES | Oc1ccc(Cl)cc1C(=O)Nc2ccc(cc2Cl)[N+]([O-])=O |
| CAS Datenbank | 50-65-7(CAS DataBase Reference) |
| EPA chemische Informationen | Niclosamide (50-65-7) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH400 (96%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]P273, P391, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 75 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Chemical: Benzamide, 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxy-Niclosamide: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - Benzamide, 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxy-: Environment tier I assessment |
| FDA-Anforderungen | Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392).Niclosamide tablets. Oral dosage form new animal drugs. Specifications and conditions of use provided for dogs.Niclosamide. New animal drugs for use in animal feeds. Conditions of use provided for laboratory mice. |
| Hazard Classes and Categories | Aquatic Acute 1 (96%) |
| Lagerbedingungen | ... stored at a temp less than 30 °Cfreezing of the tablets should be avoided. |
| Entsorgungsverfahren | 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.Niclosamide is reported to be highly stable to heat but it is hydrolized by strong alkali or acids. Recommendable methods: Incineration & landfill. Peer review: Incinerate niclosamide in a unit with effluent gas scrubbing. (Peer-review conclusions of an IRPTC expert consultation (May 1985)) |
| Wechselwirkungen | IT WAS CONCLUDED THAT CARBARYL POTENTIATED TOXICITY OF BAYER 73 TO RAINBOW TROUT BY INCREASING ITS UPTAKE FROM WATER, POSSIBLY BY EFFECTS ON GILL BLOOD FLOW OR PERMEABILITY.Niclosamide can be admin in conjunction with several other drugs ... The effectiveness of niclosamide for tapeworms of mice is enhanced when it is given in conjunction with cucurbitine or procaine.... To study the in utero developmental toxicity of these cmpd, pregnant female Wistar Albino rats received 1/50 LD50 of ametryne and niclosamide either individually or in combination on gestational days 5-15 before they were /sacrificed/ on day 20. The results showed neither mortality nor clinical no ... adverse effects in the treated dams throughout the study period. Also, no overt preimplantation losses were noted. ... Corrected maternal wt gain was significantly reduced under the influence of ametryne treatment. Gravid uterine weight and litter size were statistically reduced in dams treated with ametryne or a combination of ametryne and niclosamide. The percentage of postimplantation deaths was significantly raised under the influence of ametryne treatment (21.15%) or the combined treatment (25.45%) compared with 6.48% in untreated rats and 15.6% in niclosamide treated dams. ... Fetal morphological abnormality examination showed a pronounced incr in incidence of malformed fetuses (litters) up to 5.8% (29.4%), 6.48% (33.3%), and 7.9% (33.3%) in ametryne, niclosamide and combination treated groups, respectively, compared with 1.6% (11.1%) in the control group. The most common deformities were skeletal abnormalities in all groups studied, while the ametryne group showed external deformities as well. The results suggest the possibility of embryo/fetotoxicity of ametryne and fetotoxicity of niclosamide, at least at higher doses. |
| Ökotoxizitätswerte | LC50 Gammarus pseudolimnaeus, mature, 2,400 ug/l/96 hr at 21 °C (95% confidence limit 1,800-3,100 ug/l) /wettable powder, 70%, tested in hard water, 272 ppm calcium chloride/LC50 Orconectes, early instar, 25,000 ug/l/96 hr at 21 °C (95% confidence limit 19,000-33,000 ug/l) /wettable powder, 70%, tested in hard water, 272 ppm calcium carbonate/LC50 Palaemonetes, mature, 10,000 ug/l/96 hr at 21 °C (95% confidence limit 7,000-15,000 ug/l) /wettable powder, 70%, tested in hard water, 272 ppm calcium carbonate/LC50 Pteronarcys, second yr class, 200 ug/l/96 hr at 15 °C (95% confidence limit 130-300 ug/l) /wettable powder, 70%/For more Ecotoxicity Values (Complete) data for NICLOSAMIDE (7 total), please visit the HSDB record page. |
| Umweltverhalten | AQUATIC FATE: IT...PERSISTS /IN WATER/ FOR SEVERAL MONTHS. /ETHANOLAMINE SALT/TERRESTRIAL FATE: Based on a recommended classification scheme(1), measured Koc values from 946-1580(2) to 3111(3) (determined in sediment, pH 7.0, 20 °C) indicate that niclosamide will have low to slight mobility in soil(SRC). Results reported for water and sediment samples indicate that both aerobic and anaerobic biodegradation may be major fate processes for this compound in soil(3,SRC). Niclosamide degraded rapidly in pond and river sediments incubated under aerobic, static conditions with half-lives of 1.1 and 3.9 days, respectively(3). Niclosamide's values for vapor pressure(4) and Henry's Law constant(4,5,SRC) indicate that volatilization from dry and moist soil surfaces should not be a major fate process(SRC). Niclosamide will be susceptible to direct photolysis on soil surfacesdegradation was rapid when this compound was exposed to UV light on silica gel TLC plates and on glass slides. Less than 50% niclosamide remained after 24 hours and after 168 hours less than 5% of the parent compound remained(6).AQUATIC FATE: Intense sunlight, high pH (> 9.0), and the presence of sediment have been shown to reduce the efficacy of niclosamide treatments in water(1). Measured Koc values from 946-1580(2) to 3111(1) (determined in sediment, pH 7.0, 20 °C) indicate that niclosamide will adsorb strongly to suspended solids and sediment in the water column(1,2). Both aerobic and anaerobic biodegradation will be major fate processes for this compound in water(1,SRC). Niclosamide degraded rapidly in pond and river sediments incubated under aerobic, static conditions with half-lives of 1.1 and 3.9 days, respectively(1). Rapid disappearance of niclosamide from water above the sediment was also observed with half-lives of 3.1 and 0.83 days in water above pond and river sediment, respectively(1). 11.3, 7.2, 3.5, and 6.2% of the added 14C-niclosamide was present as CO2 after 32 days for cultures incubated under river sediment/aerobic, river sediment/anaerobic, pond sediment/aerobic, and pond sediment/anaerobic conditions, respectively(1). Aminoniclosamide is the major degradation product under both aerobic and anaerobic conditions(1).AQUATIC FATE: Niclosamide will not volatilize from water surfaces based on an estimated Henry's Law constant of 6.5X10-10 atm-cu m/mole(SRC), calculated from experimental values for vapor pressure(1) and water solubility(2). An estimated BCF value of 215(3,SRC), from a measured water solubility(2), suggests that niclosamide will bioconcentrate in aquatic organisms(SRC), according to a recommended classification scheme(4). Depuration of 14C-labeled niclosamide in rainbow trout occurred within 72 hours following exposure. Biliary concentration was high, reaching a 10,000:1 bile to water ratio within 24 hours(5). 14C-labeled niclosamide had a half-life of about 150 hours in water when it was exposed to ultraviolet light (>290 nm)(6).ATMOSPHERIC FATE: According to a suggested classification scheme(1), a measured vapor pressure of 9.9X10-9 mm Hg at 25 °C(2) indicates that niclosamide will exist mainly in the particulate phase in the ambient atmosphere. Particulate-phase niclosamide may be physically removed from the air by dry deposition(SRC). Direct photolysis of niclosamide is indicated by experiments where this compound was spotted onto silica gel plates and exposed to UV lightless than 50% of the parent compound remained after 24 hours(3). |
| Expositionspfade | Niclosamide appears to be minimally absorbed from the gastrointestinal tract - neither the drug nor its metabolites have been recovered from the blood or urine. |
| Toxizitätsübersicht | Niclosamide works by killing tapeworms on contact. Adult worms (but not ova) are rapidly killed, presumably due to uncoupling of oxidative phosphorylation or stimulation of ATPase activity. The killed worms are then passed in the stool or sometimes destroyed in the intestine. Niclosamide may work as a molluscicide by binding to and damaging DNA. |
| Soil Adsorption/Mobility | The Koc of niclosamide is estimated as approximately 1600(SRC), using a measured water solubility of 6.5 mg/L(1) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that niclosamide has low mobility in soil(SRC). Adsorption of niclosamide by sediment reached equilibrium after 4-7.5 hours of shakingan average Koc value of 3111 +/- 1552 was measured using five different sediments (pH range = 6.8-7.8organic carbon = 1.9-9.2%)(4). Bottom sediment samples from 3 rivers in the Upper Peninsula of Michigan gave Koc values at 20 °C of 3510, 946, 766, and 77.9 at pH 6.5, 7, 8, and 9 for the Cedar River, 1210, 1570, 828, and 234 at the same pH values for the Ford River, and 1920, 1580, 532, and 131 at the same pH values for the Tahquamenon River(5). |
| Human Toxicity Excerpts | Niclosamide is quite free of undesirable effects other than very occasional gastrointestinal upset.UP TO 10% OF PATIENTS MAY EXPERIENCE...MILD ABDOMINAL PAIN & NAUSEA ON DAY DRUG IS ADMIN.YOMESAN GIVEN ORALLY TO HUMANS AT 30 MG/KG DID NOT CAUSE FORMATION OF METHEMOGLOBIN.A transient erythema was the only reaction in 4 of 7 persons when niclosamide was applied to their forearms for 24 hr. 2 of 6 reacted similarly to the ethanolamine salt.For more Human Toxicity Excerpts (Complete) data for NICLOSAMIDE (10 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Niclosamide's production and use as a medication (an anthelmintic)(1) may result in its release to the environment through various waste streams(SRC). Its use as a molluscicide(1) will result in its direct release to the environment(SRC). |
| Environmental Biodegradation | A second order microbial transformation rate constant of 2.0X10-14 L/organism-hr was determined for niclosamide in natural pond waterdegradation was via microbially mediated hydrolysis of the amide(1). The biodegradability of niclosamide in soil was reported as extremely low(2). Niclosamide degraded rapidly in both pond and river sediments incubated under static conditions with half-lives of 1.1 and 3.9 days, respectively(3). Rapid disappearance of niclosamide from water above the sediment was also observed with half-lives of 3.1 and 0.83 days in water above pond and river sediment, respectively(3)degradation in autoclaved samples occurred at a very slow rate indicating a dependence on microbial activity. Aminoniclosamide is the major degradation product for this reaction, representing more than 50% of the extractable radioactivity(3). 11.3, 7.2, 3.5, and 6.2% of the added 14C-niclosamide was present as CO2 after 32 days for cultures incubated under river sediment/aerobic, river sediment/anaerobic, pond sediment/aerobic, and pond sediment/anaerobic conditions, respectivelyby 93 days, 37.7, 9.0, 6.8, and 8.7% of the total radioactivity for the same cultures was present as CO2(3). Aminoniclosamide was again the major degradation product detected in water and sediment extracts from this experimentmore aminoniclosamide was formed under anaerobic than aerobic conditions, especially during the first 64 days of incubation(3). |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Environmental Bioconcentration | An estimated BCF value of 215 was calculated for niclosamide(SRC), using a water solubility of 6.5 mg/l(1) and a recommended regression-derived equation(2). According to a classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms may be low(SRC). Depuration occurred within 72 hours for rainbow trout exposed to 14C-labeled niclosamide. Biliary concentration was high, reaching a 10,000:1 bile to water ratio in 24 hours. The metabolite formed was the glucuronide(4,5). |
| Volatilization from Water/Soil | The Henry's Law constant for niclosamide is estimated as 6.5X10-10 atm-cu m/mole(SRC) from its experimental values for vapor pressure, 9.9X10-9 mm Hg(1), and water solubility, 6.5 mg/L(2). This value indicates that niclosamide will be essentially nonvolatile from water surfaces(3,SRC). Niclosamide's values for vapor pressure(1) and Henry's Law constant(1,2,SRC) indicate that volatilization from dry and moist soil surfaces should not be a major fate process(SRC). |
| Wassergefährdungsklasse (WGK) | 2 |
| UN-Transportnummer | UN 3077 9/PG 3 |
| Zollcode | 29242990 |
| RTECS-Nr. | VN8400000 |
| R-Sätze (R) | 50 |
| Toxizität | LD50 oral in rat: 2500mg/kg |
| Sicherheitshinweise (S) | 29 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 50-65-7(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Niclosamide has been used extensively in the treatment of tapeworm infections caused by Taenia saginata, Taenia solium, Diphyllobothrium latum, Fasciolopsis buski, and Hymenolepis nana. It is an effective alternative to praziquantel for treating infections caused by T. saginata (beef tapeworm), T. solium (pork tapeworm), and D. latum (fish tapeworm) and is active against most other tapeworm infections. It is absorbed by intestinal cestodes but not nematodes.A single dose is usually adequate to produce a cure rate of 95%.With H. nana (dwarf tapeworm), a longer treatment course (up to 7 days) is necessary. Niclosamide is administered orally after the patient has fasted overnight and may be followed in 2 hours by purging (magnesium sulfate 15–30 g) to encourage complete expulsion of the cestode, especially T. solium, although this is not always considered necessary. Cure is assessed by follow-up stool examination in 3 to 5 months.With the availability of other agents, niclosamide is no longer widely used.The most widely employed agents are praziquantel and the benzimidazoles.