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
Differential effects of caffeine on dopamine and acetylcholine transmission in brain areas of drug-naive and caffeine-pretreated rats.	2002 Aug	12093592
Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens.	2002 Aug 1	12151508
Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine.	2002 Aug 15	12181566
Effects of A(1) and A(2A) adenosine receptor ligands in mouse acute models of pain.	2002 Aug 16	12147316
SCH 58261 differentially influences quinolinic acid-induced effects in striatal and in hippocampal slices.	2002 Aug 30	12208317
Effects of adenosine A1 and A2A receptor activation on the evoked release of glutamate from rat cerebrocortical synaptosomes.	2002 Jun	12023946
Differential regulation of GAD67, enkephalin and dynorphin mRNAs by chronic-intermittent L-dopa and A2A receptor blockade plus L-dopa in dopamine-denervated rats.	2002 Jun 1	11954048
Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum.	2002 Mar 1	11880527
Transducing system operated by adenosine A(2A) receptors to facilitate acetylcholine release in the rat hippocampus.	2002 Nov 1	12409002
Interactive role of adenosine and dopamine in the opiate withdrawal syndrome.	2003 Aug	12879207
Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes.	2003 Aug	12838511
Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade.	2003 Dec	14573390
Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease.	2003 Dec 9	14663021
Adenosine A2A receptors and depression.	2003 Dec 9	14663017
Adenosine A2A receptors in neuroadaptation to repeated dopaminergic stimulation: implications for the treatment of dyskinesias in Parkinson's disease.	2003 Dec 9	14663016
Modulation of glutamate release and excitotoxicity by adenosine A2A receptors.	2003 Dec 9	14663014
A2A receptors in neuroprotection of dopaminergic neurons.	2003 Dec 9	14663010
Adenosine A2A and dopamine receptor interactions in basal ganglia of dopamine denervated rats.	2003 Dec 9	14663008
Adenosine-dopamine interactions: development of a concept and some comments on therapeutic possibilities.	2003 Dec 9	14663001
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	12493612
Adenosine A(2A) antagonism increases striatal glutamate outflow in the quinolinic acid rat model of Huntington's disease.	2003 Jul 25	12850590
Adenosine promotes neuronal recovery from reactive oxygen species induced lesion in rat hippocampal slices.	2003 Mar 20	12614911
Adenosine A2A receptor antagonism increases striatal glutamate outflow in dopamine-denervated rats.	2003 Mar 7	12600692
Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats.	2003 Mar-Apr	12926542
Cyclopentyladenosine and some of its low-efficacy derivatives inhibit striatal synaptosomal release of acetylcholine to a similar degree.	2003 Nov 28	14642778
Adenosine A 2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors.	2004 Apr	15030399
Binding of the prototypical adenosine A(2A) receptor agonist CGS 21680 to the cerebral cortex of adenosine A(1) and A(2A) receptor knockout mice.	2004 Mar	14993095
Different synaptic and subsynaptic localization of adenosine A2A receptors in the hippocampus and striatum of the rat.	2005	15857695
6-(2-Furanyl)-9H-purin-2-amine derivatives as A2A adenosine antagonists.	2005 Apr 15	15808481
Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery.	2005 Jun	15653766
Adenosine A2A receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampus.	2005 May	15836618
Genetic and pharmacological inactivation of adenosine A2A receptor reveals an Egr-2-mediated transcriptional regulatory network in the mouse striatum.	2005 Sep 21	16046619
Hypoxia-induced desensitization and internalization of adenosine A1 receptors in the rat hippocampus.	2006	16442739
Forebrain adenosine A2A receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice.	2006 Dec 27	17192438
Combination of adenosine A1 and A2A receptor blocking agents induces caffeine-like locomotor stimulation in mice.	2006 Feb	16054807
Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice.	2006 Feb 15	16448647
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	16443200
Adenosine receptors as therapeutic targets.	2006 Mar	16518376
Dopamine and adenosine receptor interaction as basis for the treatment of Parkinson's disease.	2006 Oct 25	16780890
Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs.	2006 Sep 1	16793905
Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.	2007 Aug	17494861
A novel mechanism of vasoregulation: ADP-induced relaxation of the porcine isolated coronary artery is mediated via adenosine release.	2007 Feb	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 Feb	17030044
Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice.	2007 Jan	17007839
Adenosine A2A receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease.	2007 Jan 25	17123640
Synergistic effects of adenosine A2A antagonist and L-DOPA on rotational behaviors in 6-hydroxydopamine-induced hemi-Parkinsonian mouse model.	2007 Mar	17341841
3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists.	2007 Mar 15	17234414
Adenosine A2A receptor blockade prevents memory dysfunction caused by beta-amyloid peptides but not by scopolamine or MK-801.	2008 Apr	18191838
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	17934014
Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses in hippocampal interneurons.	2008 May 21	18495895

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