Dofetilide

Title: Dofetilide
CAS Registry Number: 115256-11-6
CAS Name: N-[4-[2-[Methyl[2-[4-[(methylsulfonyl)amino]phenoxy]ethyl]amino]ethyl]phenyl]methanesulfonamide
Additional Names: 1-(4-methanesulfonamidophenoxy)-2-[N-(4-methanesulfonamidophenethyl)-N-methylamino]ethane
Manufacturers' Codes: UK-68798
Trademarks: Tikosyn (Pfizer)
Molecular Formula: C19H27N3O5S2
Molecular Weight: 441.56
Percent Composition: C 51.68%, H 6.16%, N 9.52%, O 18.12%, S 14.52%
Literature References: Potassium channel blocker. Prepn: J. E. Arrowsmith et al., EP 245997; P. E. Cross et al., US 4959366 (1987, 1990 both to Pfizer); idem et al., J. Med. Chem. 33, 1151 (1990). HPLC determn in urine: D. K. Walker et al., J. Chromatogr. 568, 475 (1991). Mechanism of action study: D. Carmeliet, J. Pharmacol. Exp. Ther. 262, 809 (1992). Review of pharmacology and pharmacokinetics: H. S. Rasmussen et al., ibid. 20, Suppl. 2, S96-S105 (1992). Clinical trial in atrial fibrillation and flutter: B. L. Norgaard et al., Am. Heart J. 137, 1062 (1999); in congestive heart failure: C. Torp-Pedersen et al., N. Engl. J. Med. 341, 857 (1999).
Properties: Crystals from ethyl acetate/methanol (10:1), mp 147-149° (Cross); from hexane/ethyl acetate, mp 151-152° (Arrowsmith). Also reported as white crystalline solid, mp 161° (Rasmussen). pKa 7.0, 9.0, 9.6. Distribution coefficient (pH 7.4): 0.96. Sol in 0.1M NaOH, acetone, 0.1M HCl; very slightly sol in water, propan-2-ol.
Melting point: mp 147-149° (Cross); mp 151-152° (Arrowsmith); mp 161° (Rasmussen)
pKa: pKa 7.0, 9.0, 9.6
Therap-Cat: Antiarrhythmic (class III).
Keywords: Antiarrhythmic; Potassium Channel Blocker.
Doisynolic Acid Dolasetron DOM Domesticine Domiodol

Dofetilide
Dofetilide.png
Systematic (IUPAC) name
N-[4-(2-{[2-(4-methane sulfonamidophenoxy)ethyl] (methyl)amino}ethyl)phenyl]methanesulfonamide
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a601235
Legal status  ?
Pharmacokinetic data
Bioavailability 96% (oral)
Protein binding 60% -70%
Half-life 10 hours
Identifiers
CAS number 115256-11-6 YesY
ATC code C01BD04
PubChem CID 71329
IUPHAR ligand 2604
DrugBank DB00204
ChemSpider 64435 YesY
UNII R4Z9X1N2ND YesY
KEGG D00647 YesY
ChEBI CHEBI:4681 YesY
ChEMBL CHEMBL473 YesY
Chemical data
Formula C19H27N3O5S2 
Mol. mass 441.567 g/mol
 YesY (what is this?)  (verify)

Dofetilide is a class III antiarrhythmic agent.[1]

It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide.

Due to the pro-arrhythmic potential of dofetilide, it is only available by prescription by physicians who have undergone specific training in the risks of treatment with dofetilide. In addition, it is only available by mail order or through specially trained local pharmacies to individuals who are prescribed dofetilide by a properly registered physician.