Preladenant(SCH420814)

Cas No.:	377727-87-2
Chemical Name:	SCH-420814; SCH 420814; SCH420814
Synonyms:	SCH-420814; SCH 420814; SCH420814
SMILES:	COCCOC1=CC=C(C=C1)N2CCN(CC2)CCN3C4=C(C=N3)C5=NC(=NN5C(=N4)N)C6=CC=CO6
Formula:	C25H29N9O3
M.Wt:	503.56
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Preladenant is a potent and competitive antagonist of the human adenosine A2A receptor with a Ki of 1.1 nM and has over 1000-fold selectivity over other adenosine receptors.
In Vivo:	Preladenant (1 mg/kg) inhibits L-Dopa-induced behavioral sensitization after repeated daily administration, which suggests a reduced risk of the development of dyskinesias. Preladenant exhibits antidepressant-like profiles in models of behavioral despair, namely the mouse tail suspension test and the mouse and rat forced swim test[1]. Preladenant produces a dose-dependent reduction in parkinsonian scores at doses of 1 mg/kg (min score: 9.0) and 3 mg/kg (min score: 6.5). A subthreshold dose of Preladenant reduces minimum and mean parkinsonian scores in animals treated with 3 mg kg of L-Dopa to 5.25 and 6.88 respectively. A Wilcoxin test is used to compare individual treatments against vehicle. Preladenant (3 mg/kg), L-Dopa (3, 6, and 12 mg/kg), and the combination of Preladenant and L-Dopa (1 or 3 mg/kg+3 mg/kg) are all significantly improved on the minimum parkinsonian score. In addition, both the 12 mg/kg L-Dopa and L-Dopa+Preladenant groups are significantly improved on both minimum and mean parkinsonian scores relative to the 3 mg/kg L-Dopa group[2].
In Vitro:	Preladenant also completely antagonizes cAMP in cells expressing the recombinant human A2A receptor. Preladenant is determined to has KB values of 1.3 nM at the A2A receptor; the value is in good agreement with the Ki value determined in the radioligand binding assay. A similar functional assay with A2B receptor-expressing cells is used to demonstrate selectivity over A2B receptors. In this assay, the KB value for Preladenant is 1.2 μM, indicating that Preladenant is 923-fold selective for the A2A receptor over the A2B receptor[1].