SCH 412348

Research use only, not for human use.

SCH 412348 is a potent and highly selective A2A receptor competitive antagonist with Ki of 0.6 nM.

SCH 412348 is a potent and highly selective A2A receptor competitive antagonist with Ki of 0.6 nM; has >1000-fold selectivity over all other adenosine receptors; attenuates hypolocomotion induced by the A2AR agonist CGS-21680; exhibits antidepressant-like profiles in models of behavioral despair.Parkinson Disease Phase 2 Discontinued.

Sch412348 (SCH 412348) also completely antagonizes cAMP in cells expressing the recombinant human A2A receptor. Sch412348 is determined to have KB values of 0.3 nM, respectively at the A2A receptor; the value are in good agreement with the Ki values determined in radioligand binding assays. A similar functional assay with A2B receptor-expressing cells is used to demonstrate selectivity over A2B receptors. In this assay, the KB value for Sch412348 is 273 nM, indicating that Sch412348 is 910-fold selective for the A2A receptor over the A2B receptor.

Oral administration of Sch412348 (0.1-1 mg/kg) to rats potentiates 3,4-dihydroxy-L-phenylalanine (L-Dopa)-induced contralateral rotations after 6-hydroxydopamine lesions in the medial forebrain bundle and potently attenuates the cataleptic effects of haloperidol. Sch412348 (1 and 3 mg/kg) dose-dependently attenuates haloperidol-induced catalepsy 1 h [F(3,20)=3.9, p<0.05] and 4 h [F(3,20)=7.5, p<0.01] after dosing. Sch412348 [F(2,51) =10.6, p<0.01] (0.1-1 mg/kg) reduces immobility time in the mouse tail suspension test (TST) at 1 mg/kg. Sch412348 (SCH 412348) significantly increases activity levels in the mouse [F(4,27)=2.9, p<0.05]. Both the 0.3 and 3 mg/kg treatment groups are significantly more active than vehicle-treated mice. The 1 mg/kg group approached significance (p=0.052).

SCH412348

GPCR/G Protein

Adenosine Receptor

Adenosine Receptor

Neurological Disease

Parkinson Disease

377727-26-9

465.469

C22H21F2N9O

>98% (HPLC)

——

NC1=NC(N(CCN2CCN(C3=CC=C(F)C=C3F)CC2)N=C4)=C4C5=NC(C6=CC=CO6)=NN15

7-[2-[4-(2,4-Difluorophenyl)-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine

(-20℃)

With Ice Pack

≥ 2 years