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 2778		2.3 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14663017	Primary	Preclinical	Unknown Approved Use Unknown
Parkinson's disease 226 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
Why are A(2B) receptors low-affinity adenosine receptors? Mutation of Asn273 to Tyr increases affinity of human A(2B) receptor for 2-(1-Hexynyl)adenosine.	2000 Dec	11093773
Production of leukotrienes in a model of focal cerebral ischaemia in the rat.	2001 Aug	11498518
SCH 58261 (an adenosine A(2A) receptor antagonist) reduces, only at low doses, K(+)-evoked glutamate release in the striatum.	2001 Jun 15	11516434
Adenosine A(2a) receptor antagonists: potential therapeutic and neuroprotective effects in Parkinson's disease.	2001 Nov	15111244
Pharmacological and biochemical characterization of A3 adenosine receptors in Jurkat T cells.	2001 Sep	11522603
Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice.	2001 Sep	11522598
SCH 58261 differentially influences quinolinic acid-induced effects in striatal and in hippocampal slices.	2002 Aug 30	12208317
Diverse inhibitors of intracellular signalling act as adenosine receptor antagonists.	2002 Feb	11781134
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
Transducing system operated by adenosine A(2A) receptors to facilitate acetylcholine release in the rat hippocampus.	2002 Nov 1	12409002
Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes.	2003 Aug	12838511
Adenosine A2A receptors in neuroadaptation to repeated dopaminergic stimulation: implications for the treatment of dyskinesias in Parkinson's disease.	2003 Dec 9	14663016
SCH 58261, a selective adenosine A2A receptor antagonist, decreases the haloperidol-enhanced proenkephalin mRNA expression in the rat striatum.	2003 Jul 11	12834887
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 A 2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors.	2004 Apr	15030399
Adenosine A1 receptor blockade mimics caffeine's attenuation of ethanol-induced motor incoordination.	2004 Dec	15569276
Striatal plasticity at the network level. Focus on adenosine A2A and D2 interactions in models of Parkinson's Disease.	2004 Jul	15196505
Adenosine A2A receptor blockade differentially influences excitotoxic mechanisms at pre- and postsynaptic sites in the rat striatum.	2004 Jul 1	15197743
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
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 Oct	15350968
Effect of free radicals on adenosine A(2A) and dopamine D2 receptors in the striatum of young adult and aged rats.	2004 Oct	15234116
Blockade of adenosine A2A receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions.	2004 Sep	15296848
Facilitation of noradrenaline release by activation of adenosine A(2A) receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery.	2004 Sep 1	15306230
6-(2-Furanyl)-9H-purin-2-amine derivatives as A2A adenosine antagonists.	2005 Apr 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 Feb	15659214
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
Characterization of adenosine receptors in the human bladder carcinoma T24 cell line.	2006 Apr 24	16581066
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
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
Prevention of dyskinesia by an NMDA receptor antagonist in MPTP monkeys: effect on adenosine A2A receptors.	2006 Sep 1	16739115
Characterization of the potency, selectivity, and pharmacokinetic profile for six adenosine A2A receptor antagonists.	2007 Apr	17310264
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	17476684
A novel mechanism of vasoregulation: ADP-induced relaxation of the porcine isolated coronary artery is mediated via adenosine release.	2007 Feb	17167068
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
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	17493708
3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists.	2007 Mar 15	17234414
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	17483693
Transient inhibition of astrocytogenesis in developing mouse brain following postnatal caffeine exposure.	2007 Nov	18049373
Purinergic modulation of glutamate release under ischemic-like conditions in the hippocampus.	2007 Oct 12	17850981
Adenosine A2A receptor blockade prevents memory dysfunction caused by beta-amyloid peptides but not by scopolamine or MK-801.	2008 Apr	18191838
Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists.	2008 Jul 15	18558486
Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats.	2008 Mar	17517168
Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine.	2008 May	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 May	18297692
CNGA2 channels mediate adenosine-induced Ca2+ influx in vascular endothelial cells.	2008 May	18292397
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 `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