CVT-6883

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H21F3N6O2
Molecular Weight	446.4256
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCN1C(=O)N(CC)C2=C(NC(=N2)C3=CN(CC4=CC=CC(=C4)C(F)(F)F)N=C3)C1=O

InChI

InChIKey=KOYXXLLNCXWUNF-UHFFFAOYSA-N

InChI=1S/C21H21F3N6O2/c1-3-8-30-19(31)16-18(29(4-2)20(30)32)27-17(26-16)14-10-25-28(12-14)11-13-6-5-7-15(9-13)21(22,23)24/h5-7,9-10,12H,3-4,8,11H2,1-2H3,(H,26,27)

HIDE SMILES / InChI

Molecular Formula	C21H21F3N6O2
Molecular Weight	446.4256
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/23225885
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16841096 | https://www.ncbi.nlm.nih.gov/pubmed/18321039

CVT-6883 (GS 6201) is an A2B adenosine receptor antagonist originated by CV Therapeutics and developed by Gilead Sciences or the treatment of pulmonary diseases. In vitro studies have suggested that the activation of the A2B adenosine receptor may potentially have Proinflammatory and profibrotic effects that could be significant in the development of lung diseases. In adenosine deaminase (ADA) deficient mice, treatment with GS 6201 resulted in significantly less pulmonary inflammation, fibrosis, and alveolar airway enlargement compared with ADA-deficient mice treated with placebo. A range of doses of GS 6201 was well tolerated in healthy volunteers in a phase I multiple ascending dose trial.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenosine A2b receptor 22 Target ID: CHEMBL255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16841096	Antagonist 2778		8.3 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Asthma 241 Sources: goo.gl/g7d5Zf	Primary	Phase I 428	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 174 Sources: goo.gl/g7d5Zf	Primary	Phase I 428	Unknown Approved Use Unknown
Pulmonary fibrosis 6 Sources: goo.gl/g7d5Zf	Primary	Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677363	inconclusive [IC50 3.6626 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677363	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677363	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677363	no

Sourcing

Vendor/Aggregator	ID	URL
AChemBlock	P50927	http://www.achemblock.com/catalogsearch/result/?q=P50927
AK Scientific	SYN5470	https://aksci.com/item_detail.php?cat=SYN5470
BOC Sciences	752222-83-6	http://www.bocsci.com/description.asp?cas=752222-83-6
KeyOrganics	AS-16811	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16811
MolPort	MolPort-035-765-814	https://www.molport.com/shop/molecule-link/MolPort-035-765-814
MolPort	MolPort-044-181-422	https://www.molport.com/shop/molecule-link/MolPort-044-181-422
MuseChem	I011872	https://www.musechem.com/product/I011872.html
Princeton BioMolecular Research	PBMR221893	http://www.princetonbio.com/order_online?common_id=PBMR221893
Tocris	4727	https://www.tocris.com/search.php?Type=QuickSearch&Value=4727
eMolecules	50577902	https://orderbb.emolecules.com/search/#?query=50577902
eMolecules	85147590	https://orderbb.emolecules.com/search/#?query=85147590
mcule	MCULE-8375103059	https://mcule.com/MCULE-8375103059/

PubMed

Title	Date	PubMed
Effect of a specific and selective A(2B) adenosine receptor antagonist on adenosine agonist AMP and allergen-induced airway responsiveness and cellular influx in a mouse model of asthma.	2007 Mar	17159162
Discovery of a novel A2B adenosine receptor antagonist as a clinical candidate for chronic inflammatory airway diseases.	2008 Apr 10	18321039
Sensitive and cost-effective LC-MS/MS method for quantitation of CVT-6883 in human urine using sodium dodecylbenzenesulfonate additive to eliminate adsorptive losses.	2009 Apr 1	19282253
Activation of the macrophage A2b adenosine receptor regulates tumor necrosis factor-alpha levels following vascular injury.	2009 May	19375644
Alterations in adenosine metabolism and signaling in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.	2010 Feb 16	20169073

Patents

Sample Use Guides

In Vivo Use Guide

Experimental autoimmune encephalomyelitis (EAE) were treated via i.p. injection of CVT-6883 (0.3, 1, or 3 mg/kg, dissolved in saline) once daily from day 3 till the end of the study (day 19).

Route of Administration: Intraperitoneal

In Vitro Use Guide

Freshly isolated human dendritic cells were incubated in the presence of CVT-6883 (30, 100, or 300 nM) for 30 min before 5’-Nethylcarboxamidoadenosine (NECA). CVT-6883 significantly reduced adenosine-mediated IL-6 production by dendritic cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:11:21 UTC 2023` Edited by `admin` on `Sat Dec 16 09:11:21 UTC 2023`
Record UNII	67CKV7X08G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CVT-6883

Common Name

English

1H-PURINE-2,6-DIONE, 3-ETHYL-3,9-DIHYDRO-1-PROPYL-8-(1-((3-(TRIFLUOROMETHYL)PHENYL)METHYL)-1H-PYRAZOL-4-YL)-

Systematic Name

English

3-ETHYL-1-PROPYL-8-(1-(3-TRIFLUOROMETHYLBENZYL)-1H-PYRAZOL-4-YL)-3,7-DIHYDROPURINE-2,6-DIONE

Systematic Name

English

GS-6201

Code

English

Code System Code Type Description

FDA UNII

67CKV7X08G