PRELADENANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H29N9O3
Molecular Weight	503.5563
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COCCOC1=CC=C(C=C1)N2CCN(CCN3N=CC4=C3N=C(N)N5N=C(N=C45)C6=CC=CO6)CC2

InChI

InChIKey=DTYWJKSSUANMHD-UHFFFAOYSA-N

InChI=1S/C25H29N9O3/c1-35-15-16-36-19-6-4-18(5-7-19)32-11-8-31(9-12-32)10-13-33-23-20(17-27-33)24-28-22(21-3-2-14-37-21)30-34(24)25(26)29-23/h2-7,14,17H,8-13,15-16H2,1H3,(H2,26,29)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20878595
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19332567

Preladenant (SCH-420814) is an adenosine A(2A) receptor antagonist with a high affinity and very high selectivity for adenosine A(2A) receptors, which is being developed by Merck & Co Inc (following its acquisition of Schering-Plough Corp) for the potential treatment of Parkinson's disease. Preladenant is a potent competitive antagonist of the human A2Areceptor (Ki = 1.1 nM) and has >1000-fold selectivity over all other adenosine receptors, making this compound the most selective A2A receptor antagonist reported to date. Preladenant was being researched as a potential treatment for Parkinson's disease. Positive results were reported in Phase II clinical trials in humans, but it did not prove itself to be more effective than a placebo during Phase III trials, and so was discontinued in May 2013.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenosine A2a receptor 30 Target ID: CHEMBL251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19332567	Antagonist 2778		1.1 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 226 Sources: http://adisinsight.springer.com/drugs/800006597	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
478 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
90.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
857 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
846 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
254 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
2266 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
260 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3312 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3339 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
696 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
12.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.64 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
16.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
15.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.66 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22676397	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRELADENANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
10 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 10 mg, 2 times / day Route: oral Route: multiple Dose: 10 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28490648	unhealthy n = 200 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 200 Sources: https://pubmed.ncbi.nlm.nih.gov/28490648	Disc. AE: Adverse event... AEs leading to discontinuation/dose reduction: Adverse event (5%) Sources: https://pubmed.ncbi.nlm.nih.gov/28490648

AEs

AE	Significance	Dose	Population
Adverse event	5% Disc. AE	10 mg 2 times / day multiple, oral (unknown) Highest studied dose Dose: 10 mg, 2 times / day Route: oral Route: multiple Dose: 10 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28490648	unhealthy n = 200 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 200 Sources: https://pubmed.ncbi.nlm.nih.gov/28490648

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY100653	https://www.001chemical.com/chem/search?q=DY100653
1PlusChem LLC	1P0078E6	https://www.1pchem.com/search?query=1P0078E6
A2B Chem	AD36670	http://a2bchem.com/prod/AD36670
AChemBlock	R16063	http://www.achemblock.com/catalogsearch/result/?q=R16063
AK Scientific	4830AB	https://aksci.com/item_detail.php?cat=4830AB
AbovChem LLC	AC050943	http://www.abovchem.com/pc/en/product_list.aspx?wd=AC050943
Accela ChemBio Inc	SY031359	http://accelachem.com/cn/search.html?keyword=SY031359&attname=0
Ambeed	A120930	http://www.ambeed.com/search/Search.html?keyword=A120930
ApexBio Technology	A3735	https://www.apexbt.com/catalogsearch/result/?q=A3735
AstaTech	83199	http://astatechinc.com/CPSResult.php?CRNO=83199
BOC Sciences	377727-87-2	http://www.bocsci.com/description.asp?cas=377727-87-2
Chem Scene	CS-0999	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0999
ChemDiv	BB95-8044	http://chemistryondemand.com:8080/eShop/search_results.jsp?idnumber=BB95-8044
ChemShuttle	113976	https://www.chemshuttle.com/catalogsearch/result/?q=113976
Combi-Blocks	QK-7623	http://www.combi-blocks.com/cgi-bin/find.cgi?QK-7623
Debye Scientific	DA-42600	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-42600
Excenen	EX-A1325	http://www.excenen.com/searchresultlist.php?id=EX-A1325
KeyOrganics	DS-14327	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=DS-14327
Lab Seeker	SC-86949	http://www.labseeker.com/search.php?keywords=SC-86949&category=0
LabSeeker	SC-86949	http://www.labseeker.com/search.php?keywords=SC-86949&category=0
Matrix Scientific	96394	http://www.matrixscientific.com/096394.html
MedChem Express	HY-10889	https://www.medchemexpress.com/search.html?q=HY-10889&ft=&fa=&fp=
MolPort	MolPort-023-333-316	https://www.molport.com/shop/molecule-link/MolPort-023-333-316
Molcore	MC100653	http://www.molcore.com/CatMC100653.html
Molnova	M14304	https://www.molnova.com/en/serch-list.html?keywords=M14304
MuseChem	I003387	https://www.musechem.com/product/I003387.html
ShangHai Biochempartner	BCP000605	http://www.biochempartner.com/search_BCP000605
ShangHai Biochempartner	BCP05239	http://www.biochempartner.com/search_BCP05239
TargetMol	T4290	https://www.targetmol.com/search?keyword=T4290
Toronto Research Chemicals	P712600	https://www.trc-canada.com/product-detail/?CatNum=P712600
Wonderchem	WD060OQ	http://www.wonder-chem.com/search.html?text=WD060OQ
eMolecules	42854702	https://orderbb.emolecules.com/search/#?query=42854702
eNovation Chemicals	D374793	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D374793&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7590424843	https://mcule.com/MCULE-7590424843/

PubMed

Title	Date	PubMed
Blocking striatal adenosine A2A receptors: a new strategy for basal ganglia disorders.	2007 Jan	18221214
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	17236762
Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines.	2009 Feb 1	19109019
Characterization of the potent and highly selective A2A receptor antagonists preladenant and SCH 412348 [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] in rodent models of movement disorders and depression.	2009 Jul	19332567
Novel investigational adenosine A2A receptor antagonists for Parkinson's disease.	2009 Nov	19888872
Characterization of major degradation products of an adenosine A2A receptor antagonist under stressed conditions by LC-MS and FT tandem MS analysis.	2010 Feb	19911413
Preladenant, a novel adenosine A(2A) receptor antagonist for the potential treatment of parkinsonism and other disorders.	2010 Oct	20878595
Preladenant, a selective A(2A) receptor antagonist, is active in primate models of movement disorders.	2010 Oct	20655910
Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} ester (Lu AA47070): a phosphonooxymethylene prodrug of a potent and selective hA(2A) receptor antagonist.	2011 Feb 10	21210664
The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease.	2012 Feb	22088953

Patents

Sample Use Guides

In Vivo Use Guide

2, 5, or 10 mg tablets taken orally twice daily (BID)

Route of Administration: Oral

In Vitro Use Guide

Preladenant [1 uM] prevented the adenosine-induced process retraction in activated murine microglia

Name

Type

Language

PRELADENANT

Official Name

English

2-(Furan-2-yl)-7-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-7H-pyrazolo[4,3-E][1,2,4]triazolo[1,5-c]pyrimidin-5-amine

Systematic Name

English

SCH-420814

Code

English

SCH 420814

Code

English

Preladenant [WHO-DD]

Common Name

English

PRELADENANT [USAN]

Common Name

English

MK-3814

Code

English

preladenant [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C38149