Deferasirox(Exjade)
Deferasirox
CAS: 201530-41-8
Molecular Formula: C21H15N3O4
Deferasirox(Exjade) - Names and Identifiers
| Name | Deferasirox |
| Synonyms | Deferisirox Deferasirox Deferasirox D8 Deferasirox(Exjade) Deferasirox(CGP-72670) 4-[3,5-bis(2-hydroxyphenyl) 4-[3,5-Bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid 4-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid 4-[3,5-bis(6-oxocyclohexa-2,4-dien-1-ylidene)-1,2,4-triazolidin-1-yl]benzoic acid 4-[(3Z,5E)-3,5-bis(6-oxocyclohexa-2,4-dien-1-ylidene)-1,2,4-triazolidin-1-yl]benzoic acid |
| CAS | 201530-41-8 |
| EINECS | 685-491-5 |
| InChI | InChI=1/C21H15N3O4/c25-17-7-3-1-5-15(17)19-22-20(16-6-2-4-8-18(16)26)24(23-19)14-11-9-13(10-12-14)21(27)28/h1-12,25-26H,(H,27,28) |
Deferasirox(Exjade) - Physico-chemical Properties
| Molecular Formula | C21H15N3O4 |
| Molar Mass | 373.36 |
| Density | 1.40±0.1 g/cm3(Predicted) |
| Melting Point | 260-2620C |
| Boling Point | 672.1±65.0 °C(Predicted) |
| Flash Point | 360.287°C |
| Solubility | Soluble in water (<1 mg/ml at 25 °C), DMSO (75 mg/ml at 25 °C), ethanol (2 mg/ml |
| Vapor Presure | 0mmHg at 25°C |
| Appearance | solid |
| Color | Off-white to white |
| pKa | pKa1 4.57, pKa2 8.71, pKa3 10.56 (Nick); Also reported in H2O/DMSO (CDMSO = 0.20) as pKa1 4.61, pKa2 |
| Storage Condition | Keep in dark place,Inert atmosphere,2-8°C |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| Refractive Index | 1.699 |
| Use | A tridentate chelator that binds iron with high affinity |
Deferasirox(Exjade) - Risk and Safety
| HS Code | 2933997500 |
Deferasirox(Exjade) - Reference
| Reference Show more | 1. [IF=6.313] Yijia Yang et al."Piperlongumine Inhibits Thioredoxin Reductase 1 by Targeting Selenocysteine Residues and Sensitizes Cancer Cells to Erastin."Antioxidants-Basel. 2022 Apr;11(4):710 |
Deferasirox(Exjade) - Reference Information
| Overview | Deferasirox (deferasirox) chemical name is 4-[3,5-bis (2-hydroxyphenyl)-1,2, 4-Triazol-1-yl] benzoic acid is an iron chelating agent product developed by Novartis Pharmaceuticals, Switzerland, it is the first oral iron repellent approved by the U.S. FDA that can be used routinely. It is approved to be used in patients ≥ 2 years old and chronic iron overload caused by blood transfusion. In Europe, it is recommended as a thalassemia over 6 years old. The first-line medication for patients with iron overload is currently undergoing clinical research in China; phase II and III clinical trials and pharmacokinetic studies have shown that it has good safety and tolerability, and can significantly reduce the heart, liver iron load, easy to be accepted by patients. At the same time, it also has antifungal (such as Mucor growing in an iron-rich environment), anti-cell proliferation, anti-malaria, anti-oxidative stress injury, anti-cytotoxic-induced apoptosis and other pharmaceutical properties; it can be used for secondary The treatment of diseases such as hemochromatosis and delayed porphyria of the skin. |
| Preparation method | Using salicylic acid as raw material, salicylchloride is chlorinated by thionyl chloride to obtain salicylchloride, salicylchloride and salicylamide are in high temperature Under the condition of vacuum distillation instead of ordinary reflux method to obtain intermediates, through high temperature vacuum distillation, a large amount of low boiling substances and by-products can be evaporated, so that the mass fraction of intermediates is increased from 88.7% to 97.5%. Finally, after removing hydrochloric acid, the carboxyl phenylhydrazine hydrochloride is cyclically combined with the intermediate to prepare the deferasirox product, which reduces the operations of desalting and evaporating solvent in the post-reaction treatment, and reduces the amount of absolute ethanol The amount of use makes the operation easier. 1. Preparation of Salicylchloride (Compound 1) Add salicylic acid (13.8g,0.1 mol), 10 drops of anhydrous pyridine and 10 mL of thionyl chloride to the reaction bottle, stir for 30 min at room temperature, slowly raise the temperature to 70 ℃, stir until almost no hydrogen chloride gas is released, then raise the temperature to 80 ℃, stir for 3 h. The remaining thionyl chloride is evaporated under reduced pressure to obtain a light yellow liquid, cooled to precipitate crystals, and used directly for the next reaction. Preparation of 2.2-(2-hydroxyphenyl)-[1,3] benzoxazinone (Compound 2) Add salicylamide (13.7g,0.1 mol) and compound 1 prepared by the previous reaction to the reaction bottle equipped with a distillation device, heat to 180 ℃, and distill under reduced pressure for 3 h while reacting to remove the water obtained by the reaction. 50 mL of anhydrous ethanol is added under melting (heat preservation), solid yellow product is precipitated, filtered, anhydrous ethanol is recrystallized to obtain 16.8g of yellow product with 70.3% yield and mp 210~213 ℃. 3. Preparation of p-Carboxyphenylhydrazine Hydrochloride (Compound 3) Add p-aminobenzoic acid (6.85g,0.05 mol) and distilled water 10 mL into a 250 mL three-mouth flask, stir into a paste, add 12.5 mL concentrated hydrochloric acid dropwise below 5 ℃, cool to 5 ℃ in an ice-salt bath, slowly add sodium nitrite (3.5g,0.05 mol) is dissolved in a saturated solution with a small amount of water (8g) for diazotization reaction, the reaction temperature is controlled to be lower than 5 ℃, stirring is continued for 30 min after dropping, then the diazonium salt solution is poured into a solution of sodium sulfite (25.2g,0.2 mol) cooled to 5 ℃ in advance and dissolved in water (100 mL), stirring at this temperature for 30 min, heating to 80 ℃, and keeping the temperature for 1.5 h, the orange-red solution turns slightly yellow, cools to room temperature, slowly adds hydrochloric acid to acidify to pH 3, and the p-carboxyphenylhydrazine hydrochloride is precipitated, filtered, and dried for later use to obtain 8.3g of white product with 88.3% yield. 4. Preparation of deferasirox Compound 3(3.8g,0.02 mol) is adjusted to pH value to 6 with 30% NaOH, stirred, left to stand and stratified, and the water layer is separated. The oil layer is p-carboxyphenylhydrazine. The oil layer was placed in a flask, compound 2(5.0g,0.02 mol) was added, and refluxed in absolute ethanol solution (75 mL) for 2 h. Cooling, crystallization, filtration, washing with 10 mL ice ethanol, drying, ethanol-water recrystallization to obtain 6.3g of yellowish product with 84.45% yield. Fig. 1 shows the synthesis route of deferasirox |
| pharmacological effects | DFS has antifungal effects (such as Mucor growing in an iron-rich environment), anti-cell proliferation effects, anti-malaria, anti-oxidative stress damage, anti-cytotoxic induced apoptosis and other pharmacological effects. 1.DFS and fungal infection iron are the substances on which fungi depend for survival. It plays a very important role in the growth and toxicity of fungi. The antifungal effect of iron chelating agent may be to remove iron necessary for fungal growth, so as to achieve the purpose of treating fungal infection. 2.DFS and cell proliferation iron play a very important role in the process of cell proliferation, and iron chelating agent may have anti-cell proliferation properties, which is associated with iron chelating agent may become a new anti-cancer agent for tumor treatment. |
| Pharmacokinetics | DFS is a tridentate iron chelating agent, which is combined with ferric ions in a ratio of 2:1 to form a complex, which is excreted from feces, Thereby reducing the storage of iron in the body. Due to the persistence of DFS in plasma, plasma non-transferrin binding iron can be continuously reduced, and the iron formed by toxicity in the body can be directly eliminated. The main metabolic pathway of DFS is glucoside acidification to generate metabolites M3 (acyl glucuronide) and M6 (2-O-glucuronide). |
| adverse reactions | large doses of DFS can cause some acute adverse reactions, such as gastrointestinal symptoms (15%) and rash (11%). However, patients who interrupt treatment due to these symptoms are rare. For patients with renal insufficiency, DFS can cause creatinine level to increase, and 38% patients can increase creatinine level by more than 33%, but the creatinine level increase caused by DFS generally does not exceed the upper limit of normal and has not been reported to cause progressive renal disease. After DFS dose reduction, creatinine levels in 13% patients returned to normal or remained stable. <1% of patients have hearing impairment (hearing loss, hearing loss) and eye diseases (lens opacity, cataract, elevated intraocular pressure and retinopathy). Therefore, it is recommended to perform auditory and visual examinations (including slit lamp examination and fundus examination) every year before and during iron removal therapy. Once found, DFS should be discontinued. The common side effects of deferasirox in Chinese thalassemia patients are: rash, abdominal pain, diarrhea, elevated transaminase, elevated serum muscle intoxication, most of which are mild, and no serious adverse reactions are found. Deferasirox can cause kidney injury and gastrointestinal bleeding. Therefore, it is recommended to detect creatinine clearance twice before the start of treatment, once a week within 1 month at the beginning of treatment, and once a month thereafter. Gastrointestinal bleeding is a common adverse reaction of the drug. Gastrointestinal bleeding may be fatal in elderly patients with advanced malignant hematological diseases or thrombocytopenia, and these patients are unlikely to benefit from the drug. Deferasirox may lead to serious adverse reactions of liver failure. Patients must regularly monitor their liver function every month during the medication process. Once there is an unexplained, persistent or progressive increase in serum aminotransferase levels, the use of deferasirox should be adjusted or discontinued. |
| application | 1.DFS can be used to treat reversible renal insufficiency caused by Fanconi syndrome. 2. For the treatment of secondary hemochromatosis. 3. It can be used to treat delayed cutaneous porphyria. 4. For the treatment of myelodysplastic syndrome. 5. It is used to treat iron overload caused by blood transfusion in patients with chronic anemia aged 2 years and above. (2015-09-18) |
| precautions | patients with deturarox allergy are prohibited. |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-09 15:16:48
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