Deferasirox
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| 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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| Identifiers | |
| CAS number | 201530-41-8 |
| ATC code | V03AC03 |
| PubChem | 5493381 |
| ChemSpider | 4591431 |
| Chemical data | |
| Formula | C21H15N3O4 |
| Mol. mass | 373.362 g/mol |
| SMILES | eMolecules & PubChem |
| Pharmacokinetic data | |
| Bioavailability | 70% |
| Protein binding | 99% |
| Metabolism | Hepatic glucuronidation |
| Half life | 8 to 16 hours |
| Excretion | Fecal (84%) and renal (8%) |
| Therapeutic considerations | |
| Licence data | |
| Pregnancy cat. | |
| Legal status | |
| Routes | Oral |
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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
[edit] Properties of deferasirox
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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 molecule 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.
[edit] Synthesis
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].
[edit] References
- ^ a b c Choudhry VP, Naithani R (2007). "Current status of iron overload and chelation with deferasirox". Indian J Pediatr 74 (8): 759–64. doi:. PMID 17785900. Free full text
- ^ Yang LP, Keam SJ, Keating GM (2007). "Deferasirox : a review of its use in the management of transfusional chronic iron overload". Drugs 67 (15): 2211–30. PMID 17927285.
- ^ a b United States Food and Drug Administration (November 9, 2005). "FDA Approves First Oral Drug for Chronic Iron Overload". Press release. http://www.fda.gov/bbs/topics/news/2005/NEW01258.html. Retrieved 2007-10-31.
- ^ Stefan Steinhauser, Uwe Heinz, Mark Bartholomä, Thomas Weyhermüller, Hanspeter Nick, Kaspar Hegetschweiler (2004). "Complex Formation of ICL670 and Related Ligands with FeIII and FeII". European Journal of Inorganic Chemistry 2004 (21): 4177-4192. doi:.]
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