ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors 2,4-PyriMidinediaMine, 5-[5-iodo-4-Methoxy-2-(1-Methylethyl)phenoxy]-

2,4-PyriMidinediaMine, 5-[5-iodo-4-Methoxy-2-(1-Methylethyl)phenoxy]-

Product Name2,4-PyriMidinediaMine, 5-[5-iodo-4-Methoxy-2-(1-Methylethyl)phenoxy]-
CAS865305-30-2
MFC14H17IN4O2
MW400.21
EINECS
MOL File865305-30-2.mol

Chemical Properties

Boiling point	510.2±60.0 °C(Predicted)
Density	1.619±0.06 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO : ≥ 32 mg/mL (79.96 mM)
pka	6.89±0.10(Predicted)
form	Solid
color	Light brown to brown
InChI	InChI=1S/C14H17IN4O2/c1-7(2)8-4-11(20-3)9(15)5-10(8)21-12-6-18-14(17)19-13(12)16/h4-7H,1-3H3,(H4,16,17,18,19)
InChIKey	AATPYXMXFBBKFO-UHFFFAOYSA-N
SMILES	C1(N)=NC=C(OC2=CC(I)=C(OC)C=C2C(C)C)C(N)=N1

Usage And Synthesis

Description

AF-353 is a noncompetitive dual antagonist of the purinoreceptors P2X₃ and P2X_2/3 (IC₅₀s = 10 and 79.4 nM, respectively). It is selective for P2X₃ and P2X_2/3 over P2X₁, P2X₂, P2X₄, P2X₅, and P2X₇ (IC₅₀ = >10 μM for all). It inhibits calcium flux in CHO-K1 cells expressing the rat P2X₃ receptor and in 1321N1 cells expressing the human P2X₃ and P2X_2/3 receptors (IC₅₀s = 8.91, 8.71, and 38.9 nM, respectively). AF-353 decreases the electrical signals in the detrusor, but not striated, muscle of the bladder in female rats.

Uses

AF-353 (Ro-4) is a potent, selective and orally bioavailable P2X3/P2X2/3 receptor antagonist, with a pIC50 of 8.0 for both human and rat P2X3, and with a pIC50 of 7.3 for human P2X2/3[1][2].

in vivo

AF-353 (Ro-4) does not compromise oxygen levels or cardiac function^[2].
AF-353 (Ro-4) (10 mg/kg, 20 mg/kg; i.v.; for 4-6 hours) inhibits the purinergic response in both normal and spinal cord-injured (SCI) rats^[2].
AF-353 (Ro-4) (10 mg/kg, 20 mg/kg; i.v.; for 4-6 hours) also reduces the inter-contractile interval in normal but not in SCI rats; however, the frequency of non-voiding (NVC) in SCI rats is significantly reduced^[2].

Animal Model:	Female Sprague-Dawley rats (250–300 g) bearing SCI^[2]
Dosage:	10 mg/kg, 20 mg/kg
Administration:	Intravenous injection; interval of 90 minutes, for 4 hours to 6 hours
Result:	Significantly reduced purinergic response in both normal and SCI rats.

IC 50

P2X3 Receptor

References

[1] Gever JR, et al. AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist. Br J Pharmacol. 2010 Jul;160(6):1387-1398. DOI:10.1111/j.1476-5381.2010.00796.x
[2] Munoz A, et al. Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3receptors. BJU Int. 2012 Oct;110(8 Pt B):E409-414. DOI:10.1111/j.1464-410X.2012.11189.x

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