944261-79-4

Basic information

• Product Name: 5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5-dimethoxyphenylamide
• Synonyms: 5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5-dimethoxyphenylamide;A 803467;5-(4-Chlorophenyl)-N-(3,5-dimethoxyphenyl)-2-furancarboxamide;5-(4-Chlorophenyl)-N-(3,5-dimethoxyphenyl)-;5-4(-Chlorophenyl)-N-(3,5-diMethoxyphenyl)furan-2-carboxaMide;2-FurancarboxaMide,5-(4-chlorophenyl)-N-(3,5-diMethoxyphenyl)-;5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5;A-803467, >=99%
• CAS NO: 944261-79-4
• Molecular Formula: C₁₉H₁₆ClNO₄
• Molecular Weight: 357.791
• Product Categories: Sodium channel;Ion Channels;Amines;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Inhibitors
• Mol File: 944261-79-4.mol

Chemical Properties

• Melting Point: 128-130?C
• Boiling Point: 450.6 °C at 760 mmHg
• Flash Point: 226.3 °C
• Appearance: white to tan/
• Density: 1.294 g/cm³
• Vapor Pressure: 2.6E-08mmHg at 25°C
• Refractive Index: 1.611
• Storage Temp.: Store at +4°C
• Solubility: DMSO: >10mg/mL
• PKA: 11.72±0.70(Predicted)
• 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.
• CAS DataBase Reference: 5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5-dimethoxyphenylamide(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5-dimethoxyphenylamide(944261-79-4)
• EPA Substance Registry System: 5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5-dimethoxyphenylamide(944261-79-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 944261-79-4(Hazardous Substances Data)

Usage

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.

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

InChI:InChI=1/C19H16ClNO4/c1-23-15-9-14(10-16(11-15)24-2)21-19(22)18-8-7-17(25-18)12-3-5-13(20)6-4-12/h3-11H,1-2H3,(H,21,22)

Upstream product

• 585-70-6 5-bromo-furan-2-carboxylic acid 
• 57753-81-8 5-(4-chlorophenyl)furan-2-carboxamide 
• 20469-65-2 1-bromo-3,5-dimethoxybenzene 
• 57753-80-7 5-(4-chloro-phenyl)-furan-2-carbonyl chloride 
• 10272-07-8 3.5-dimethoxyaniline 

Relevant articles and documents

T-BuXPhos: A highly efficient ligand for Buchwald-Hartwig coupling in water

An efficient and versatile 'green' catalytic system for the Buchwald-Hartwig cross-coupling reaction in water is reported. In an aqueous micellar medium, the combination of t-BuXPhos with [(cinnamyl)PdCl]2 showed excellent performance for coupling arylbromides or chlorides with a large set of amines, amides, ureas and carbamates. The method is functional-group tolerant, proceeds smoothly (30 to 50 °C) and provides rapid access to the target compounds in good to excellent isolated yields. When applied to the synthesis of a known NaV1.8 modulator, this method led to a significant improvement of the E-factor in comparison with classical organic synthesis. the Partner Organisations 2014.

Discovery and biological evaluation of 5-aryl-2-furfuramides, potent and selective blockers of the Nav1.8 sodium channel with efficacy in models of neuropathic and inflammatory pain

Nav1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an NavL8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Nav1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 v1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed > 100-fold selectivity versus human sodium (Na v1.2, Nav1.5, Nav1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and 27 dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models.