CAS 113559-13-0|E-4031

Introduction：Basic information about CAS 113559-13-0|E-4031, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. E-4031 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Articles25
6. Synonyms

Common Name	E-4031
CAS Number	113559-13-0	Molecular Weight	474.444
Density	/	Boiling Point	561.7ºC at 760 mmHg
Molecular Formula	C₂₁H₂₉Cl₂N₃O₃S	Melting Point	/
MSDS	ChineseUSA	Flash Point	293.5ºC

Names

Name	N-[4-[1-[2-(6-methylpyridin-2-yl)ethyl]piperidine-4-carbonyl]phenyl]methanesulfonamide,dihydrochloride
Synonym	More Synonyms

E-4031 BiologicalActivity

Description	E-4031 is a benzenesulfonamide antiarrhythmic agent; blocks the ATP-sensitive potassium channel.IC50 value:Target: K+ channel blockerin vitro: Dofetilide and E-4031 induced EADs or TdP in all assays (50-83%), and the induction correlated with a significant increase in beat-to-beat variability of repolarization [1]. E-4031 (0.1 mumol/L) significantly prolonged cycle length and action potential duration, depolarized maximum diastolic potential, and reduced both the upstroke velocity of the action potential and the diastolic depolarization rate [2].in vivo: E-4031 in doses of 0.01 and 0.1 mg/kg that can provide the plasma concentrations effectively to inhibit IKrin vitro significantly delayed the repolarization beyond the initiation of diastole, resulting in the inversion of electro-mechanical coupling, which provides an ideal proarrhythmic substrate, while the durations of left ventricular systole and diastole remained the same [3]. Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia [4].
Related Catalog	Signaling Pathways >>Membrane Transporter/Ion Channel >>Potassium ChannelResearch Areas >>Cardiovascular Disease
References	[1]. Nalos L, et al. Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five screening models of pro-arrhythmia reveals lack of specificity of isolated cardiomyocytes. Br J Pharmacol. 2012 Jan;165(2):467-78. [2]. Verheijck EE, et al. Effects of delayed rectifier current blockade by E-4031 on impulse generation in single sinoatrial nodal myocytes of the rabbit. Circ Res. 1995 Apr;76(4):607-15. [3]. Izumi-Nakaseko H, et al. Effects of selective IKr channel blockade by E-4031 on ventricular electro-mechanical relationship in the halothane-anesthetized dogs. Eur J Pharmacol. 2014 Oct 5;740:263-70. [4]. Izumi D, et al. Effects of bepridil versus E-4031 on transmural ventricular repolarization and inducibility of ventricular tachyarrhythmias in the dog. Pacing Clin Electrophysiol. 2010 Aug;33(8):950-9.

Description

E-4031 is a benzenesulfonamide antiarrhythmic agent; blocks the ATP-sensitive potassium channel.IC50 value:Target: K+ channel blockerin vitro: Dofetilide and E-4031 induced EADs or TdP in all assays (50-83%), and the induction correlated with a significant increase in beat-to-beat variability of repolarization [1]. E-4031 (0.1 mumol/L) significantly prolonged cycle length and action potential duration, depolarized maximum diastolic potential, and reduced both the upstroke velocity of the action potential and the diastolic depolarization rate [2].in vivo: E-4031 in doses of 0.01 and 0.1 mg/kg that can provide the plasma concentrations effectively to inhibit IKrin vitro significantly delayed the repolarization beyond the initiation of diastole, resulting in the inversion of electro-mechanical coupling, which provides an ideal proarrhythmic substrate, while the durations of left ventricular systole and diastole remained the same [3]. Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia [4].

Related Catalog

Signaling Pathways >>Membrane Transporter/Ion Channel >>Potassium ChannelResearch Areas >>Cardiovascular Disease

References

[1]. Nalos L, et al. Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five screening models of pro-arrhythmia reveals lack of specificity of isolated cardiomyocytes. Br J Pharmacol. 2012 Jan;165(2):467-78.

[2]. Verheijck EE, et al. Effects of delayed rectifier current blockade by E-4031 on impulse generation in single sinoatrial nodal myocytes of the rabbit. Circ Res. 1995 Apr;76(4):607-15.

[3]. Izumi-Nakaseko H, et al. Effects of selective IKr channel blockade by E-4031 on ventricular electro-mechanical relationship in the halothane-anesthetized dogs. Eur J Pharmacol. 2014 Oct 5;740:263-70.

[4]. Izumi D, et al. Effects of bepridil versus E-4031 on transmural ventricular repolarization and inducibility of ventricular tachyarrhythmias in the dog. Pacing Clin Electrophysiol. 2010 Aug;33(8):950-9.

Chemical & Physical Properties

Boiling Point	561.7ºC at 760 mmHg
Molecular Formula	C₂₁H₂₉Cl₂N₃O₃S
Molecular Weight	474.444
Flash Point	293.5ºC
Exact Mass	473.130676
PSA	87.75000
LogP	5.59460
Vapour Pressure	1.21E-12mmHg at 25°C
InChIKey	ZQBNWMFBOSOOLX-UHFFFAOYSA-N
SMILES	Cc1cccc(CCN2CCC(C(=O)c3ccc(NS(C)(=O)=O)cc3)CC2)n1.Cl.Cl
Storage condition	2-8℃

Safety Information

Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
RIDADR	NONH for all modes of transport

Articles25

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Wound Repair Regen. 23 , 797-806, (2015)

Previous studies indicate that ion channels are mediators of bioelectricity promoting wound closure/regeneration in nonmammalian, lower vertebrate systems. The role of ion channels however in regenera...

Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

Anesthesiology 120(6) , 1400-13, (2014)

Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct e...

Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.

Toxicol. Sci. 148 , 241-60, (2015)

More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Current in vitro testing strategies predominantly take the form...

Synonyms

Methanesulfonamide, N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl]-, hydrochloride (1:2)

N-[4-({1-[2-(6-Methyl-2-pyridinyl)ethyl]-4-piperidinyl}carbonyl)phenyl]methanesulfonamide dihydrochloride

E-4031

N-(4-(1-(2-(6-methylpyridin-2-yl)ethyl)piperidine-4-carbonyl)phenyl)methanesulfonamide dihydrochloride

N-[4-({1-[2-(6-Methylpyridin-2-yl)ethyl]piperidin-4-yl}carbonyl)phenyl]methanesulfonamide dihydrochloride

MFCD01754739

E 4031 dihydrochloride

PDZ1 Domain inhibitor peptide

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