5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5<br>-dimethoxyphenylamide Property

Melting point:

128-130?C

Boiling point:

450.6±45.0 °C(Predicted)

Density 

1.294±0.06 g/cm3(Predicted)

storage temp. 

room temp

solubility 

DMSO: >10mg/mL

form 

powder

pka

11.72±0.70(Predicted)

color 

white to tan

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.

Safety

Hazard Codes 

Xn

Risk Statements 

22

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P330Rinse mouth.

5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5<br>-dimethoxyphenylamide Chemical Properties,Usage,Production

Description

Na_v1.8 is a tetrodotoxin-resistant (TTX-R) sodium channel with high activation threshold and slow inactivating kinetics that is highly expressed in small-diameter sensory neurons and has been implicated in signaling various types of pain. A-803467 is a sodium channel blocker with high-affinity and selectivity for inhibiting human Na_v1.8 sodium channels (IC₅₀ = 8 nM when stimulated at half-maximal inactivation and IC₅₀ = 79 nM at a resting state). This compound is unusual in that it blocks hNav1.8 at negative resting membrane potentials (many small molecule sodium channel blockers show a reduced affinity for the resting state) and does not demonstrate significant frequency-dependent block during a 10 Hz pulse train. A-803467 dose-dependently reduces behavioral responses in a variety of neuropathic and inflammatory pain models.

Chemical Properties

White Solid

Uses

A selective NaV1.8 sodium channel blocker, reduces behavioral measures of chronic pain. Analgesic.

General Description

The small molecule A-803467 is a potent and selective Nav1.8 sodium channel blocker. Nav1.8 is a tetrodotoxin-resistant (TTX-R) sodium channel that contributes to pain sensation by transmitting pain stimuli in peripheral sensory neurons; blockage of this channel by A-803467 reduces pain with varying effectiveness in a number of different models. A-803467 has been used to further understand the role of Nav1.8 in transmitting pain stimuli and also can be used as an analgesic.

Biological Activity

Selective blocker of Na V 1.8 channels (IC 50 values are 8, 2450, 6740, 7340 and 7380 nM for hNa V 1.8, hNa V 1.3, hNa V 1.7, hNa V 1.5 and hNa V 1.2 channels respectively). Shows no significant activity against TRPV1, P2X 2/3 , Ca V 2.2 and KCNQ2/3 channels. Antinociceptive; potently attenuates mechanical allodynia in two models of neuropathic pain following i.p. administration.

Biochem/physiol Actions

A-803467 blocks Nav1.8 in both half-maximal inactive and resting states with an IC50 of 8 nM and IC50 of 79 nM, respectively. A-803467 is over 100-fold more selective vs. human Nav1.2, 1.3, 1.5 and 1.7.

storage

+4°C

References

1) Jarvis et al. (2007), A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat; Proc. Natl. Acad. Sci. USA, 104 8520 2) McGaraughty et al. (2008), A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic rats; J. Pharmacol. Exp. Ther., 324 1204