Dofetilide

Names

[ Name ]:
Dofetilide

[Synonym ]:
N-[4-[2-[Methyl[2-[4-[(methylsulfonyl)amino]phenoxy]ethyl]amino]ethyl]phenyl]methanesulfon Amide
Dofetilidum
Xelide
N-[4-[2-[2-[4-(methanesulfonamido)phenoxy]ethyl-methylamino]ethyl]phenyl]methanesulfonamide
MFCD00869707
Dofetilide
1-MSPMPE
b-((p-Methanesulfonamidophenethyl)methylamino)methanesulfono-p-phenetidide
N-(4-{2-[Methyl(2-{4-[(methylsulfonyl)amino]phenoxy}ethyl)amino]ethyl}phenyl)methanesulfonamide
Dofetilida
Methanesulfonamide, N-[4-[2-[methyl[2-[4-[(methylsulfonyl)amino]phenoxy]ethyl]amino]ethyl]phenyl]-
Tikosyn

Biological Activity

[Description]:

Dofetilide(Tikosyn) is a class III antiarrhythmic agent.Target: Potassium ChannelIn patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality [1]. dofetilide preferentially blocks open (or activated) channels and that the fast inactivation may competitively slow the binding kinetics. Dofetilide acts as a slow-onset/slow-offset open channel blocker of this current at nanomolar concentrations [2].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Cardiovascular Disease

[References]

[1]. Maisch, B., et al., [Pregnancy and cardiomyopathies]. Herz, 2003. 28(3): p. 196-208.

[2]. Snyders, D.J. and A. Chaudhary, High affinity open channel block by dofetilide of HERG expressed in a human cell line. Mol Pharmacol, 1996. 49(6): p. 949-55.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
614.1±65.0 °C at 760 mmHg

[ Melting Point ]:
147-1490C

[ Molecular Formula ]:
C₁₉H₂₇N₃O₅S₂

[ Molecular Weight ]:
441.565

[ Flash Point ]:
325.2±34.3 °C

[ Exact Mass ]:
441.139221

[ PSA ]:
121.57000

[ LogP ]:
1.56

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.614

[ Storage condition ]:
Store at RT

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: PB0478000

CHEMICAL NAME :: Methanesulfonamide, N-(4-(2-(methyl(2-(4-((methylsulfonyl)amino)phenoxy)e thyl)amino)ethyl) phenyl)-

CAS REGISTRY NUMBER :: 115256-11-6

LAST UPDATED :: 199806

DATA ITEMS CITED :: 3

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 22050 ug/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 53,168,1996

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 11025 ug/kg

SEX/DURATION :: female 13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 53,168,1996

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 44100 ug/kg

SEX/DURATION :: female 14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 53,168,1996

Safety Information

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H360

[ Precautionary Statements ]:
P201-P308 + P313

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
R36/37/38:Irritating to eyes, respiratory system and skin .

[ Safety Phrases ]:
26-37/39

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Synchronous systolic subcellular Ca2+-elevations underlie ventricular arrhythmia in drug-induced long QT type 2.

Circ. Arrhythm. Electrophysiol. 8 , 703-12, (2015)

Repolarization delay is a common clinical problem, which can promote ventricular arrhythmias. In myocytes, abnormal sarcoplasmic reticulum Ca(2+)-release is proposed as the mechanism that causes early...

The Link between Inactivation and High-Affinity Block of hERG1 Channels.

Mol. Pharmacol. 87 , 1042-50, (2015)

Block of human ether-à-go-go-related gene 1 (hERG1) K(+) channels by many drugs delays cardiac repolarization, prolongs QT interval, and is associated with an increased risk of cardiac arrhythmia. Pre...

Relevance of calmodulin/CaMKII activation for arrhythmogenesis in the AV block dog.

Heart Rhythm 9(11) , 1875-83, (2012)

The calcium-dependent signaling molecules calcineurin and calcium/calmodulin-dependent protein kinase II (CaMKII) both have been linked to decompensated hypertrophy and arrhythmias. CaMKII is also bel...