SCH-58261

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16780890 | https://www.ncbi.nlm.nih.gov/pubmed/9535988 | https://www.ncbi.nlm.nih.gov/pubmed/9179373 | http://adisinsight.springer.com/drugs/800025245 | https://clinicaltrials.gov/ct2/show/NCT01227265 | https://www.ncbi.nlm.nih.gov/pubmed/25513815

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenosine receptor A2a 15 Target ID: P29274 Gene ID: 135.0 Gene Symbol: ADORA2A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8632302 \| https://www.ncbi.nlm.nih.gov/pubmed/9179373	Antagonist 2849		2.3 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Depression 240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14663017	Primary	Preclinical	Unknown Approved Use Unknown
Parkinson's disease 232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16780890 https://www.ncbi.nlm.nih.gov/pubmed/25513815	Primary	Preclinical	Unknown Approved Use Unknown
Low blood pressure 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9535988	Primary	Preclinical	Unknown Approved Use Unknown
Myocardial ischemia due to sepsis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27757725	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists.	2008-07-15	18558486
Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses in hippocampal interneurons.	2008-05-21	18495895
Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine.	2008-05	18384819
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.	2008-05	18297692
CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells.	2008-05	18292397
Adenosine A2A receptor blockade prevents memory dysfunction caused by beta-amyloid peptides but not by scopolamine or MK-801.	2008-04	18191838
Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats.	2008-03	17517168
Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses.	2008-01-10	18184569
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.	2008-01	17934014
Transient inhibition of astrocytogenesis in developing mouse brain following postnatal caffeine exposure.	2007-11	18049373
Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH 58261 in R6/2 Huntington's disease mice.	2007-11	17720507
Purinergic modulation of glutamate release under ischemic-like conditions in the hippocampus.	2007-10-12	17850981
Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.	2007-08	17494861
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.	2007-08	17476684
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.	2007-07	17493708
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.	2007-05	17483693
Characterization of the potency, selectivity, and pharmacokinetic profile for six adenosine A2A receptor antagonists.	2007-04	17310264
3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists.	2007-03-15	17234414
Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines.	2007-03-01	17236762
Synergistic effects of adenosine A2A antagonist and L-DOPA on rotational behaviors in 6-hydroxydopamine-induced hemi-Parkinsonian mouse model.	2007-03	17341841
A novel mechanism of vasoregulation: ADP-induced relaxation of the porcine isolated coronary artery is mediated via adenosine release.	2007-02	17167068
Tonic adenosine A1 and A2A receptor activation is required for the excitatory action of VIP on synaptic transmission in the CA1 area of the hippocampus.	2007-02	17030044
Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease.	2007-01-25	17123640
Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice.	2007-01	17007839
Forebrain adenosine A2A receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice.	2006-12-27	17192438
Dopamine and adenosine receptor interaction as basis for the treatment of Parkinson's disease.	2006-10-25	16780890
Glial cell line-derived neurotrophic factor (GDNF) enhances dopamine release from striatal nerve endings in an adenosine A2A receptor-dependent manner.	2006-10-03	16935271
Increased density and synapto-protective effect of adenosine A2A receptors upon sub-chronic restraint stress.	2006-09-15	16797134
Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs.	2006-09-01	16793905
Prevention of dyskinesia by an NMDA receptor antagonist in MPTP monkeys: effect on adenosine A2A receptors.	2006-09-01	16739115
Central adenosine signaling plays a key role in centrally mediated hypotension in conscious aortic barodenervated rats.	2006-07	16595736
Characterization of adenosine receptors in the human bladder carcinoma T24 cell line.	2006-04-24	16581066
Adenosine receptors as therapeutic targets.	2006-03	16518376
The selective A2A receptor antagonist SCH 58261 protects from neurological deficit, brain damage and activation of p38 MAPK in rat focal cerebral ischemia.	2006-02-16	16443200
Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice.	2006-02-15	16448647
Combination of adenosine A1 and A2A receptor blocking agents induces caffeine-like locomotor stimulation in mice.	2006-02	16054807
Hypoxia-induced desensitization and internalization of adenosine A1 receptors in the rat hippocampus.	2006	16442739
Genetic and pharmacological inactivation of adenosine A2A receptor reveals an Egr-2-mediated transcriptional regulatory network in the mouse striatum.	2005-09-21	16046619
Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery.	2005-06	15653766
Adenosine A2A receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampus.	2005-05	15836618
6-(2-Furanyl)-9H-purin-2-amine derivatives as A2A adenosine antagonists.	2005-04-15	15808481
Co-localization and functional interaction between adenosine A(2A) and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum.	2005-02	15659214
Mediators of coronary reactive hyperaemia in isolated mouse heart.	2005-02	15655499
Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat.	2005	15857695
A2B adenosine receptor activity is reduced in neutrophils from patients with systemic sclerosis.	2005	15743465
Adenosine A1 receptor blockade mimics caffeine's attenuation of ethanol-induced motor incoordination.	2004-12	15569276
Regulation of A2B adenosine receptor functioning by tumour necrosis factor a in human astroglial cells.	2004-12	15569261
Adenosine receptors involved in modulation of noradrenaline release in isolated rat tail artery.	2004-11-03	15507216
Glutamate efflux from human cerebrocortical slices during ischemia: vesicular-like mode of glutamate release and sensitivity to A(2A) adenosine receptor blockade.	2004-11	15527822
Adenosine and glutamate extracellular concentrations and mitogen-activated protein kinases in the striatum of Huntington transgenic mice. Selective antagonism of adenosine A2A receptors reduces transmitter outflow.	2004-10	15350968

Patents

Sample Use Guides

In Vivo Use Guide

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 `Mon Mar 31 22:07:12 GMT 2025` Edited by `admin` on `Mon Mar 31 22:07:12 GMT 2025`
Record UNII	4309023MAH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SCH-58261

Common Name

English

SCH 58261

Preferred 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

Code System Code Type Description

EPA CompTox

DTXSID80166799