Deferasirox

Title: Deferasirox
CAS Registry Number: 201530-41-8
CAS Name: 4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid
Manufacturers' Codes: ICL-670; ICL-670A; CGP-72670
Trademarks: Exjade (Novartis)
Molecular Formula: C21H15N3O4
Molecular Weight: 373.36
Percent Composition: C 67.56%, H 4.05%, N 11.25%, O 17.14%
Literature References: Orally active tridentate iron chelator. Prepn: R. Lattmann, P. Acklin, WO 9749395; eidem, US 6465504 (1997, 2002 both to Novartis); U. Heinz et al., Angew. Chem. Int. Ed. 38, 2568 (1999). HPLC determn in plasma: M. C. Rouan et al., J. Chromatogr. B 755, 203 (2001). Iron complex formation study: S. Steinhauser et al., Eur. J. Inorg. Chem. 2004, 4177. Pharmacology: C. Hershko et al., Blood 97, 1115 (2001). Clinical pharmacokinetics: R. Galanello et al., J. Clin. Pharmacol. 43, 565 (2003). Clinical trial in thalassemia: E. Nisbet-Brown et al., Lancet 361, 1597 (2003). Review of structure activity: H. Nick et al., Curr. Med. Chem. 10, 1065-1076 (2003); of preclinical and clinical experience: M. D. Cappellini, Best Prac. Res. Clin. Haematol. 18, 289-298 (2005).
Properties: Crystals from ethanol, mp 264-265°. Soly in water at 25° (mg/ml): 0.4 (pH 7.40). pKa1 4.57, pKa2 8.71, pKa3 10.56 (Nick). Also reported in H2O/DMSO (CDMSO = 0.20) as pKa1 4.61, pKa2 10.12, pKa3 12.08 (Steinhauser). Partition coefficient (octanol/water): 6.3 (pH 7.40). uv max (H2O/DMSO, pH < 2): 284 nm (e 1.5 ´ 104).
Melting point: mp 264-265°
pKa: pKa1 4.57, pKa2 8.71, pKa3 10.56 (Nick); Also reported in H2O/DMSO (CDMSO = 0.20) as pKa1 4.61, pKa2 10.12, pKa3 12.08 (Steinhauser)
Log P: Partition coefficient (octanol/water): 6.3 (pH 7.40)
Absorption maximum: uv max (H2O/DMSO, pH < 2): 284 nm (e 1.5 ´ 104)
Therap-Cat: Chelating agent (iron).
Keywords: Chelating Agent.
Deferiprone Defibrotide Deflazacort Defosfamide DEHP

Deferasirox
Deferasirox.svg
Systematic (IUPAC) name
[4-[(3Z,5E)-3,5-bis(6-oxo-1-cyclohexa-2,4-
dienylidene)-1,2,4-triazolidin-1-yl]benzoic acid
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 YesY
ATC code V03AC03
PubChem CID 5493381
DrugBank DB01609
ChemSpider 4591431 YesY
UNII V8G4MOF2V9 YesY
KEGG D03669 YesY
ChEMBL CHEMBL550348 N
Chemical data
Formula C21H15N3O4 
Mol. mass 373.362 g/mol
 N (what is this?)  (verify)

Deferasirox (marketed as Exjade[1]) is a rationally-designed[2] 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.[2][3] It is the first oral medication approved in the USA for this purpose.[4]

It was approved by the United States Food and Drug Administration (FDA) in November 2005.[2][4] According to FDA (May 2007), renal failure and cytopenias have been reported in patients receiving deferasirox oral suspension tablets. It is approved in the European Union by the European Medicines Agency (EMA) for children 6 years and older for chronic iron overload from repeated blood transfusions.[5][6][7]