448895-37-2

Basic information

• Product Name: NS1643
• Synonyms: N,N'-Bis[2-hydroxy-5-(trifluoromethyl)phenyl]urea
• CAS NO: 448895-37-2
• Molecular Formula: C15H10F6N2O3
• Molecular Weight: 380.243
• Mol File: 448895-37-2.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 342.311°C at 760 mmHg
• Flash Point: 160.824°C
• Appearance: white to off-white/
• Density: 1.627g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.589
• Storage Temp.: Store at +4°C
• Solubility: DMSO: ≥20mg/mL
• PKA: 6.84±0.13(Predicted)
• CAS DataBase Reference: NS1643(CAS DataBase Reference)
• NIST Chemistry Reference: NS1643(448895-37-2)
• EPA Substance Registry System: NS1643(448895-37-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36
• Safety Statements: 26
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 448895-37-2(Hazardous Substances Data)

Usage

Uses

NS 1643 is a human ether-a-go-go-related gene 1 potassium channel (KCNH2) activator.

Biological Activity

Human ether-a-go-go related gene (hERG) K + channel activator (EC 50 = 10.5 μ M). Exhibits different molecular mechanisms of action at hERG1 and hERG2 channels. Displays antiarrhythmic activity in vitro .

InChI:InChI=1/C15H10F6N2O3/c16-14(17,18)7-1-3-11(24)9(5-7)22-13(26)23-10-6-8(15(19,20)21)2-4-12(10)25/h1-6,24-25H,(H2,22,23,26)

Upstream product

• 349-65-5 2-Methoxy-5-trifluoromethyl-aniline 
• 6064-14-8 1,3-bis(2-methoxy-5-trifluoromethylphenyl)urea 

Relevant articles and documents

Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643)

The cardiac action potential is generated by a concerted action of different ion channels and transporters. Dysfunction of any of these membrane proteins can give rise to cardiac arrhythmias, which is particularly true for the repolarizing potassium channels. We suggest that an increased repolarization current could be a new antiarrhythmic principle, because it possibly would attenuate afterdepolarizations, ischemic leak currents, and reentry phenomena. Repolarization of the cardiac myocytes is crucially dependent on the late rapid delayed rectifier current (IKr) conducted by ether-a-go-go-related gene (ERG) potassium channels. We have developed the diphenylurea compound 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) and tested whether this small organic molecule could increase the activity of human ERG (HERG) channels expressed heterologously. In Xenopus laevis oocytes, NS1643 increased both steady-state and tail current at all voltages tested. The EC50 value for HERG channel activation was 10.5 μM. These results were reproduced on HERG channels expressed in mammalian human embryonic kidney 293 cells. In guinea pig cardiomyocytes, studied by patch clamp, application of 10 μM NS1643 activated IKr and significantly decreased the action potential duration to 65% of the control values. The effect could be reverted by application of the specific HERG channel inhibitor 4′-[[1-[2-(6-methyl-2- pyridyl)ethyl]-4-piperidinyl]carbonyl]-methanesulfonanilide (E-4031) at 100 nM. Application of NS1643 also resulted in a prolonged postrepolarization refractory time. Finally, cardiomyocytes exposed to NS1643 resisted reactivation by small depolarizing currents mimicking early afterdepolarizations. In conclusion, HERG channel activation by small molecules such as NS1643 increases the repolarization reserve and presents an interesting new antiarrhythmic approach. Copyright