RO-3

• CAT Number: I010670
• CAS Number: 1026582-88-6
• Molecular Formula: C16H22N4O2
• Molecular Weight: 302.37
• Purity: ≥95%
• Synonyms: 5-[(4,5-dimethoxy-2-propan-2-ylphenyl)methyl]pyrimidine-2,4-diamine
• InChI: InChI=1S/C16H22N4O2/c1-9(2)12-7-14(22-4)13(21-3)6-10(12)5-11-8-19-16(18)20-15(11)17/h6-9H,5H2,1-4H3,(H4,17,18,19,20)
• InChIKey: PYNPWUIBJMVRIG-UHFFFAOYSA-N
• SMILES: CC(C)C1=CC(=C(C=C1CC2=CN=C(N=C2N)N)OC)OC

RO-3 is a potent, CNS-penetrant, and orally active P2X3 and P2X2/3 antagonist with pIC50s of 5.9 and 7.0 for human homomultimeric P2X3 and heteromultimeric P2X2/3 receptors, respectively. RO-3 shows selectivity for P2X3 and P2X2/3 over all other functional homomultimeric P2X receptors (IC50 >10 μM at P2X1,2,4,5,7)[1].
In a guinea pig ureter-afferent nerve preparation, and mouse bladder-pelvic nerve preparation, RO-3 dose-dependently reduces afferent nerve activity induced by distension or α,β-meATP[1].
RO-3 has activity in several rodent models of pain, as well as in cystometry models optimized to measure various parameters associated with sensory regulation of the micturition reflex[1].
RO-3 has moderate to high metabolic stability in rat and human hepatocytes and liver microsomes, and is highly permeable, orally bioavailable (14%), and has a reasonable in vivo plasma half-life (t1/2=0.41 h) in rats[1].

Reference

[1]. Ford AP, et al. Purinoceptors as therapeutic targets for lower urinary tract dysfunction. Br J Pharmacol. 2006;147 Suppl 2(Suppl 2):S132-S143.
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