| Identification | Back Directory | [Name]
2,4-PyriMidinediaMine, 5-[5-iodo-4-Methoxy-2-(1-Methylethyl)phenoxy]- | [CAS]
865305-30-2 | [Synonyms]
Ro 4
AF 353
CS-2469
CHEMBL526307
AF-353 (Ro-4)
CHEMBL526307;AF 353;AF353
5-[5-Iodo-4-methoxy-2-(1-methylethyl)phenoxy]-2,4-pyrimidinediamine
2,4-PyriMidinediaMine, 5-[5-iodo-4-Methoxy-2-(1-Methylethyl)phenoxy]-
5-{[5-iodo-2-(1-Methylethyl)-4-(Methyloxy)phenyl]oxy}-2,4-pyriMidinediaMine
5-[5-iodo-4-methoxy-2-(1-methylethyl)phenoxy]-2,4-pyrimidinediamine hydrochloride Ro 4 hydrochloride | [Molecular Formula]
C14H17IN4O2 | [MDL Number]
MFCD18782750 | [MOL File]
865305-30-2.mol | [Molecular Weight]
400.21 |
| Chemical Properties | Back Directory | [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) | [form ]
Solid | [pka]
6.89±0.10(Predicted) | [color ]
Light brown to brown |
| Hazard Information | Back Directory | [Description]
AF-353 is a noncompetitive dual antagonist of the purinoreceptors P2X3 and P2X2/3 (IC50s = 10 and 79.4 nM, respectively).1,2 It is selective for P2X3 and P2X2/3 over P2X1, P2X2, P2X4, P2X5, and P2X7 (IC50 = >10 μM for all).2 It inhibits calcium flux in CHO-K1 cells expressing the rat P2X3 receptor and in 1321N1 cells expressing the human P2X3 and P2X2/3 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.3 | [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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