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Deferoxamin
DESFEROXAMINE · dfoa · taone · entaone · ba33112 · desferin · desferex · desferan
Identifikatoren & physikalische Daten
| CAS No. | 70-51-9 |
|---|---|
| Summenformel | C25H48N6O8 |
| Durchschnittliche Molmasse | 560,7 g/mol |
| Monoisotopische Masse | 560,3533625 g/mol |
| SMILES | CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN |
| InChIKey | UBQYURCVBFRUQT-UHFFFAOYSA-N |
| PubChem CID | 2973 |
| ChEMBL | CHEMBL556 |
| ChEBI | CHEBI:4356 |
| EC No. | 200-738-5 |
| DTXSID | DTXSID7022887 |
| Lokaler Name | Deferoxamin |
Chemische & physikalische Eigenschaften
| XLogP | -2,1 |
|---|---|
| Polarare Oberfläche (TPSA) | 206 |
| H-Brücken-Donoren | 6 |
| H-Brücken-Akzeptoren | 9 |
| Frei drehbare Bindungen | 23 |
| Schwere Atome | 39 |
| Formalladung | 0 |
| Komplexität | 739 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15 |
| Lipide | Fatty Acyls [FA] -> Fatty amides [FA08] -> N-acyl amines [FA0802] |
| LogP (Verteilungskoeffizient) | -2.2-1.52 |
| Löslichkeit | 9.90e-02 g/L |
| Human Drugs | Breast FeedingLactationChelating AgentsIron Chelating AgentsAntidotes and other substances used in poisonings > Specific |
| Schmelzpunkt | MP: 138-140 °C /MONOHYDRATE/172-175 °C /HYDROCHLORIDE/148-149 °C /METHANESULFONATE/MP: 180-182 °C /N-ACETYL DERIV/138 - 140 °C139°C |
| Physical Description | Solid |
| Stability/Shelf Life | RECONSTITUTED SOLN ARE STABLE FOR 2 WK @ ROOM TEMP /MESYLATE/ |
| Collision Cross Section | 228.86 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Other Experimental Properties | CRYSTALS FROM DIL ALC /MONOHYDRATE/CRYSTALS FROM SLIGHTLY ACIDIC METHANOL /HYDROCHLORIDE/CRYSTALS FROM DIL ALC /METHANESULFONATE/CRYSTALS FROM N-PROPANOL /N-ACETYL DERIV/ |
| Siedepunkt | 627.9°C (rough estimate) |
| Dichte | 1.2216 (rough estimate) |
| Brechungsindex | 1.5540 (estimate) |
| Lagerbedingungen | -20°C |
| Aggregatzustand | Solid |
| pKa (Säurekonstante) | 9.08±0.50(Predicted) |
| Farbe | White to off-white |
| Hauptanwendungen | pharmaceutical |
| InChIKey | UBQYURCVBFRUQT-UHFFFAOYSA-N |
| SMILES | C(=O)(N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN)CCC(=O)NCCCCCN(O)C(=O)C |
| EPA chemische Informationen | Deferoxamine (70-51-9) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH302 (97.1%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 69 reports by companies from 3 notifications to the ECHA C&L Inventory. |
|---|---|
| Regulatorische Informationen | Status: Active Update: 07-06-2016 https://echa.europa.eu/registration-dossier/-/registered-dossier/17782 |
| Hazard Classes and Categories | Acute Tox. 4 (97.1%) |
| Wechselwirkungen | THE CONCOMITANT ORAL ADMINISTRATION OF ASCORBIC ACID (0.5 TO 1 G TWICE DAILY) SEEMS TO IMPROVE THE CHELATING ACTION OF DEFEROXAMINE IN HEMOCHROMATOSIS, PARTICULARLY IF THERE IS A VITAMIN C DEFICIENCY. |
| Hepatotoxicity | In large clinical trials, elevations in serum aminotransferase levels were rare in patients receiving deferoxamine and instances of acute, clinically apparent liver injury were not reported. Patients with transfusion related iron overload often have concurrent chronic hepatitis B or C, and elevations of serum aminotransferase levels during chelation therapy may be due to natural fluctuations in the underlying chronic liver disease activity. Nevertheless, elevations in serum aminotransferase levels and “hepatic dysfunction” are listed as potential adverse events in product labels for deferoxamine. After an early report of hepatitis occurring in patient on hemodialysis receiving deferoxamine to reduce aluminum levels, there have been no further published instances of clinically apparent liver injury that have been convincingly linked to deferoxamine therapy. |
| Unerwünschte Wirkungen | Chronic deferoxamine therapy can lead to sensorineural hearing loss and retinopathy. Though the mechanism of ocular injury is not well understood, it appears to partially occur due to damage to the retinal pigment epithelium, which can lead to decreased visual acuity, visual field defects, and color vision defects. Hearing and vision loss can be reversible if the patient discontinues the drug early in the course. Growth retardation can also occur in children receiving deferoxamine treatment, and clinicians should monitor patients for appropriate growth velocity over time. |
| Toxizitätsübersicht | Patients tolerate deferoxamine well, and there is no specific antidote for the medication. The precautions and dose reductions are described elsewhere in this paper. |
| Human Toxicity Excerpts | PAIN & INDURATION MAY OCCUR @ SITE OF IM INJECTION. OTHER UNTOWARD EFFECTS INCL ERYTHEMA, FLUSHING, DIARRHEA, BLURRING OF VISION, ABDOMINAL DISCOMFORT, MUSCULAR SPASMS IN LEGS, ITCHING, TACHYCARDIA, & FEVER. IN LONG TERM THERAPY, VARIOUS ALLERGIC REACTIONS, INCL ANAPHYLAXIS, HAVE BEEN REPORTED. /MESYLATE/REACTIONS HAVE INCLUDED HYPOTENSION, PROBABLY DUE TO HISTAMINE RELEASE (ESP DURING IV ADMIN), SKIN RASHES, & GI IRRITATION. OCCASIONAL CASES OF CATARACT FORMATION IN MAN HAVE BEEN REPORTED...A WOMAN WITH BETA-THALASSAEMIA INTERMEDIA, AND IRON OVERLOAD FOLLOWING MANY YEAR'S THE COURSE OF THIS TREATMENT SHE DEVELOPED TINNITUS, WHICH WAS CONSIDERED TO BE A RARE COMPLICATION OF THE USE OF THIS CHELATING AGENT.DESFERRIOXAMINE WAS GIVEN INTRAVENOUSLY, AT HIGHER DOSES THAN PREVIOUSLY REPORTED, TO COUNTER THE EFFECTS OF TRANSFUSION-INDUCED IRON OVERLOAD IN FOUR PATIENTS WITH BETA THALASSAEMIA MAJOR. IN TWO OF THEM RETINAL ABNORMALITIES DEVELOPED, PRESENTING WITH NIGHT BLINDNESS AND FIELD DEFECTS, WHICH IMPROVED ON WITHDRAWAL OF THE DRUG. |
| Drug Induced Liver Injury | Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)deferoxamineDesferal®Chelating agentsNot Applicableno-DILI-concern |
| Non-Human Toxicity Excerpts | DOGS TOLERATE SINGLE IV DOSES UP TO 100 MG/KG WITH SIGNS SUGGESTING TRANSIENT HYPOTENSION....IT HAS PRODUCED OPACITIES IN CRYSTALLINE LENS IN DOGS, CATS, & RATS WHEN GIVEN BY DAILY SC INJECTION FOR LONG PERIODS @ DOSAGES SO LARGE THAT THEY PRODUCE SEVERE GASTROENTERITIS.INJECTION OF 28.5% SOLN SUBCONJUNCTIVALLY HAS CAUSED SLIGHT CHEMOSIS & HYPEREMIA. ... INJECTION OF 50 MG SUBCONJUNCTIVALLY WAS TOLERATED BY EYES OF MONKEYS......50 MG INJECTED SUBCONJUNCTIVALLY IN RABBITS EVERY 1-3 DAYS FOR SEVERAL MO WAS TOLERATED...BUT 200 MG SUBCONJUNCTIVALLY IN RABBITS CAUSED REDN IN RESPONSE OF PUPIL TO LIGHT, CONGESTION OF UVEA, & EXUDATIVE DETACHMENT OF CHOROID & RETINA...INTRAVITREAL INJECTIONS OF 5 MG DEFEROXAMINE IN RABBITS PROVED VERY TOXIC, CAUSING WIDESPREAD HEMORRHAGIC NECROSIS, PARTICULARLY AFFECTING RODS & CONES OF RETINA & EXTINGUISHING ELECTRORETINOGRAM. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| Wassergefährdungsklasse (WGK) | WGK 3 |
| Toxizität | LD50 oral in mouse: 1340mg/kg |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 70-51-9(Hazardous Substances Data) |
Anwendungen & Verwendung
Beschreibung
Deferoxamine was introduced in the 1960s for chelation of iron. It is synthesized by removing a central iron molecule from ferrioxamine B, a compound obtained from the microorganism Streptomyces pilosus. Deferoxamine binds to iron from ferritin and forms ferrioxamine, a very stable and water-soluble chelate with a characteristic reddish color.
Verwenden
Deferoxamine is used for the treatment of both acute iron intoxication and chronic iron overload due to transfusiondependent anemias. It has also been used in trials for malaria treatment and for aluminum chelation in hemodialysis patients. Studies of a rat model of intracerebral hemorrhage have noted that deferoxamine treatment reduced oxidative stress from iron release, indicating a possible role in preventing damage associated with hemorrhagic strokes.