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Details

Stereochemistry ACHIRAL
Molecular Formula C18H15N7O
Molecular Weight 345.358
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SCH-58261

SMILES

NC1=NC2=C(C=NN2CCC3=CC=CC=C3)C4=NC(=NN14)C5=CC=CO5

InChI

InChIKey=UTLPKQYUXOEJIL-UHFFFAOYSA-N
InChI=1S/C18H15N7O/c19-18-22-16-13(11-20-24(16)9-8-12-5-2-1-3-6-12)17-21-15(23-25(17)18)14-7-4-10-26-14/h1-7,10-11H,8-9H2,(H2,19,22)

HIDE SMILES / InChI

Molecular Formula C18H15N7O
Molecular Weight 345.358
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

SCH-58261 is an antagonist of the Adenosine A2A receptor with a Kd of 2.3 nM. It was initially identified and developed by Schering-Plough as a potential treatment for neurological conditions such as Parkinson's Disease and Depression. However, the compound suffered from poor solubility and is not active when orally dosed. SCH-58261 became the scaffold for the development of Preladenant (SCH 412348), which did progress to Phase III clinical trials before being discontinued. There has also been an investigation of SCH-58261 as a treatment of hypotension in rat models.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P29274
Gene ID: 135.0
Gene Symbol: ADORA2A
Target Organism: Homo sapiens (Human)
2.3 nM [Kd]
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
Interactive role of adenosine and dopamine in the opiate withdrawal syndrome.
2003 Aug
Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease.
2003 Dec 9
Adenosine A2A receptors in neuroadaptation to repeated dopaminergic stimulation: implications for the treatment of dyskinesias in Parkinson's disease.
2003 Dec 9
Modulation of glutamate release and excitotoxicity by adenosine A2A receptors.
2003 Dec 9
A2A receptors in neuroprotection of dopaminergic neurons.
2003 Dec 9
Adenosine A2A and dopamine receptor interactions in basal ganglia of dopamine denervated rats.
2003 Dec 9
Adenosine-dopamine interactions: development of a concept and some comments on therapeutic possibilities.
2003 Dec 9
Pharmacological analysis of calcium responses mediated by the human A3 adenosine receptor in monocyte-derived dendritic cells and recombinant cells.
2003 Feb
The selective A2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behavior and ischemic brain damage induced by permanent focal ischemia in the rat.
2003 Jan 10
Adenosine A2A receptor antagonism increases striatal glutamate outflow in dopamine-denervated rats.
2003 Mar 7
Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats.
2003 Mar-Apr
Cyclopentyladenosine and some of its low-efficacy derivatives inhibit striatal synaptosomal release of acetylcholine to a similar degree.
2003 Nov 28
Regulation of A2B adenosine receptor functioning by tumour necrosis factor a in human astroglial cells.
2004 Dec
Adenosine A2A receptor blockade differentially influences excitotoxic mechanisms at pre- and postsynaptic sites in the rat striatum.
2004 Jul 1
Glutamate efflux from human cerebrocortical slices during ischemia: vesicular-like mode of glutamate release and sensitivity to A(2A) adenosine receptor blockade.
2004 Nov
Adenosine receptors involved in modulation of noradrenaline release in isolated rat tail artery.
2004 Nov 3
Blockade of adenosine A2A receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions.
2004 Sep
Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat.
2005
6-(2-Furanyl)-9H-purin-2-amine derivatives as A2A adenosine antagonists.
2005 Apr 15
Adenosine A2A receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampus.
2005 May
Genetic and pharmacological inactivation of adenosine A2A receptor reveals an Egr-2-mediated transcriptional regulatory network in the mouse striatum.
2005 Sep 21
Characterization of adenosine receptors in the human bladder carcinoma T24 cell line.
2006 Apr 24
Forebrain adenosine A2A receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice.
2006 Dec 27
The selective A2A receptor antagonist SCH 58261 protects from neurological deficit, brain damage and activation of p38 MAPK in rat focal cerebral ischemia.
2006 Feb 16
Central adenosine signaling plays a key role in centrally mediated hypotension in conscious aortic barodenervated rats.
2006 Jul
Dopamine and adenosine receptor interaction as basis for the treatment of Parkinson's disease.
2006 Oct 25
Glial cell line-derived neurotrophic factor (GDNF) enhances dopamine release from striatal nerve endings in an adenosine A2A receptor-dependent manner.
2006 Oct 3
Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs.
2006 Sep 1
Increased density and synapto-protective effect of adenosine A2A receptors upon sub-chronic restraint stress.
2006 Sep 15
Characterization of the potency, selectivity, and pharmacokinetic profile for six adenosine A2A receptor antagonists.
2007 Apr
Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.
2007 Aug
Adenosine A2A receptor antagonists improve deficits in initiation of movement and sensory motor integration in the unilateral 6-hydroxydopamine rat model of Parkinson's disease.
2007 Aug
A novel mechanism of vasoregulation: ADP-induced relaxation of the porcine isolated coronary artery is mediated via adenosine release.
2007 Feb
A2A adenosine-receptor-mediated facilitation of noradrenaline release in rat tail artery involves protein kinase C activation and betagamma subunits formed after alpha2-adrenoceptor activation.
2007 Jul
Synergistic effects of adenosine A2A antagonist and L-DOPA on rotational behaviors in 6-hydroxydopamine-induced hemi-Parkinsonian mouse model.
2007 Mar
Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines.
2007 Mar 1
3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists.
2007 Mar 15
Effects of the adenosine A2A receptor antagonist SCH 58621 on cyclooxygenase-2 expression, glial activation, and brain-derived neurotrophic factor availability in a rat model of striatal neurodegeneration.
2007 May
Transient inhibition of astrocytogenesis in developing mouse brain following postnatal caffeine exposure.
2007 Nov
Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH 58261 in R6/2 Huntington's disease mice.
2007 Nov
Purinergic modulation of glutamate release under ischemic-like conditions in the hippocampus.
2007 Oct 12
Adenosine A2A receptor blockade prevents memory dysfunction caused by beta-amyloid peptides but not by scopolamine or MK-801.
2008 Apr
Brainstem phosphorylated extracellular signal-regulated kinase 1/2-nitric-oxide synthase signaling mediates the adenosine A2A-dependent hypotensive action of clonidine in conscious aortic barodenervated rats.
2008 Jan
Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses.
2008 Jan 10
Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists.
2008 Jul 15
Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats.
2008 Mar
Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine.
2008 May
Blockade of globus pallidus adenosine A(2A) receptors displays antiparkinsonian activity in 6-hydroxydopamine-lesioned rats treated with D(1) or D(2) dopamine receptor agonists.
2008 May
CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells.
2008 May
Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses in hippocampal interneurons.
2008 May 21
Patents

Sample Use Guides

Normotensive rats were dosed with 0.1, 1, 3, and 10 mg/kg of SCH-58261 and monitored for changes in blood pressure (BP) and heart rate (HR). Maximum effect on systolic-BP and diastolic-BP were +19 +/- 3 mmHg and +16 +/- 2 mmHg respectively. Maximal HR increase was + 85 +/- 5 bpm. These effects were recorded 50 minutes after injection and had a half-life of 60 minutes.
Route of Administration: Intraperitoneal
In Vitro Use Guide
Chinese Hamster Ovary Cells stably expressing the human A2A adenosine receptor were pre-treated with adenosine deaminase and then incubated for 30 min, 25 degC, pH 7.4 with a [3H]-SCH 58261 concentration ranging from 0.0625 to 64 nM. The specific binding of [3H]-SCH 58261 was rapid, saturable, and increased linearly with respect to protein concentration over the range of 25 ± 250 mg of protein/assay. Binding equilibrium was achieved within 5 min and stable for at least 4 h. A Kd value of 2.3 nM was determined for the A2a adenosine receptors.
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:29:49 GMT 2023
Edited
by admin
on Sat Dec 16 08:29:49 GMT 2023
Record UNII
4309023MAH
Record Status Validated (UNII)
Record Version
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Name Type Language
SCH-58261
Common Name English
5-AMINO-7-(2-PHENYLETHYL)-2-(2-FURYL)-PYRAZOLO(4,3-E)-1,2,4-TRIAZOLO(1,5-C)PYRIMIDINE
Systematic Name English
SCH 58261
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID80166799
Created by admin on Sat Dec 16 08:29:49 GMT 2023 , Edited by admin on Sat Dec 16 08:29:49 GMT 2023
PRIMARY
FDA UNII
4309023MAH
Created by admin on Sat Dec 16 08:29:49 GMT 2023 , Edited by admin on Sat Dec 16 08:29:49 GMT 2023
PRIMARY
PUBCHEM
176408
Created by admin on Sat Dec 16 08:29:49 GMT 2023 , Edited by admin on Sat Dec 16 08:29:49 GMT 2023
PRIMARY
WIKIPEDIA
SCH-58261
Created by admin on Sat Dec 16 08:29:49 GMT 2023 , Edited by admin on Sat Dec 16 08:29:49 GMT 2023
PRIMARY
CAS
160098-96-4
Created by admin on Sat Dec 16 08:29:49 GMT 2023 , Edited by admin on Sat Dec 16 08:29:49 GMT 2023
PRIMARY
Related Record Type Details
TARGET->WEAK INHIBITOR
Ki
TARGET -> INHIBITOR
Highly selective over hA2B Ki = 1110 nM.
Ki
Related Record Type Details
ACTIVE MOIETY