| Systematic (IUPAC) name | |
|---|---|
| [4-[(3Z,5E)-3,5-bis(6-oxo-1-cyclohexa-2,4- dienylidene)-1,2,4-triazolidin-1-yl]benzoic acid |
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| Clinical data | |
| Licence data | EMA:Link |
| Pregnancy cat. | C(AU) B(US) |
| Legal status | POM (UK) ℞-only (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 70% |
| Protein binding | 99% |
| Metabolism | Hepatic glucuronidation |
| Half-life | 8 to 16 hours |
| Excretion | Fecal (84%) and renal (8%) |
| Identifiers | |
| CAS number | 201530-41-8 |
| ATC code | V03AC03 |
| PubChem | CID 5493381 |
| DrugBank | DB01609 |
| ChemSpider | 4591431 |
| UNII | V8G4MOF2V9 |
| KEGG | D03669 |
| ChEMBL | CHEMBL1201122 |
| Chemical data | |
| Formula | C21H15N3O4 |
| Mol. mass | 373.362 g/mol |
| SMILES | eMolecules & PubChem |
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Deferasirox (marketed as Exjade) is a rationally-designed[1] oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias.[1][2] It is the first oral medication approved in the USA for this purpose.[3]
It was approved by the United States Food and Drug Administration (FDA) in November 2005.[1][3] According to FDA (May 2007), renal failure and cytopenias have been reported in patients receiving deferasirox oral suspension tablets.
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The half-life of deferasirox is between 8 and 16 hours allowing once a day dosing. Two molecules of deferasirox are capable of binding to 1 atom of iron which are subsequently eliminated by fecal excretion. Its low molecular weight and high lipophilicity allows the drug to be taken orally unlike desferoxamine which has to be administered by IV route (intravenous infusion). Together with deferiprone, deferasirox seems to be capable of removing iron from cells (cardiac myocytes and hepatocytes) as well as removing iron from the blood.
Deferasirox can be prepared from simple commercially available starting materials (salicylic acid, salicylamide and 4-hydrazinobenzoic acid) in the following two-step synthetic sequence:
The condensation of salicyloyl chloride (formed in situ from salicylic acid and thionyl chloride) with salicylamide under dehydrating reaction conditions results in formation of 2-(2-hydroxyphenyl)-1,3(4H)-benzoxazin-4-one. This intermediate is isolated and reacted with 4-hydrazinobenzoic acid in the presence of base to give 4-(3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl)benzoic acid (Deferasirox).[4]
Deferasirox was the #2 drug on the list of 'Most frequent suspected drugs in reported patient deaths' compiled by the Institute for Safe Medical Practices in 2009. There were 1320 deaths reported, perhaps explained by an update to the ADE data of Novartis, and a new boxed warning about gastrointestinal haemorrhage as well as kidney and liver failure. [5]
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