GS 6201

Names

[ Name ]:
GS 6201

[Synonym ]:
1H-Purine-2,6-dione,3-ethyl-3,7-dihydro-1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]-1H-pyrazol-4-yl]-(9CI)
1H-Purine-2,6-dione,3-ethyl-3,9-dihydro-1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]-1H-pyrazol-4-yl]
3-ETHYL-1-PROPYL-8-(1-(3-(TRIFLUOROMETHYL)BENZYL)-1H-PYRAZOL-4-YL)-1H-PURINE-2,6(3H,8H)-DIONE
3-ethyl-1-propyl-8-(1-{[3-(trifluoromethyl)phenyl]methyl}pyrazol-4-yl)-1,3,7-trihydropurine-2,6-dione
CVT 6883
8-(1-(3-(trifluoromethyl)benzyl)-1H-pyrazol-4-yl)-3-ethyl-1-propyl-1H-purine-2,6(3H,7H)-dione

Biological Activity

[Description]:

GS-6201 (CVT-6883) is a selective adenosine A2B receptor antagonist. GS-6201 displays high affinity and selectivity for the human adenosine A2B receptors (Ki=22 nM)[1]. GS-6201 reduces caspase-1 activity in the heart, and attenuates cardiac remodeling after acute myocardial infarction (AMI) in the mouse[2]. GS-62013 attenuates the airway reactivity induced by NECA, AMP, or allergen in sensitized mice[3].

[Related Catalog]:

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> Adenosine Receptor

[Target]

Ki: 22 nM (human A2B receptors), 1070 nM (human A3 receptors), 1940 nM (human A1 receptors), 3280 nM (human A2A receptors)[1]

[In Vivo]

GS-6201 (CVT-6883) (4 mg/kg; i.p.; every 12 h for 14 days) significantly reduces IL-6, TNF-α, E-selectin, ICAM-1, and VCAM plasma levels[2]. GS-6201 (4 mg/kg; i.p.; every 12 h for 14 days) leads to a significant attenuation of left and right ventricular enlargement and dysfunction at 7 days, which was maintained at 14 days and also at 28 days[2]. GS-6201 (2 mg/kg; p.o.) treatment shows the Cmax, dAUC and t1/2 are 1110 ng/mL, 6500 ng h/mL, and 4.25 hours, respectively[1]. Animal Model: Adult out-bred male CD1 mice (8-12 weeks of age, AMI model)[2] Dosage: 4 mg/kg Administration: i.p.; every 12 h for 14 days Result: Significantly reduced IL-6, TNF-α, E-selectin, ICAM-1, and VCAM plasma levels. Animal Model: Sprague-Dawley rats[1] Dosage: 2 mg/kg Administration: p.o. (Pharmacokinetic Analysis) Result: The Cmax, dAUC and t1/2 were 1110 ng/mL, 6500 ng h/mL, and 4.25 hours, respectively.

[References]

[1]. Elzein E, et al. Discovery of a novel A2B adenosine receptor antagonist as a clinical candidate for chronic inflammatory airway diseases. J Med Chem. 2008 Apr 10;51(7):2267-78.

[2]. Toldo S, et al. GS-6201, a selective blocker of the A2B adenosine receptor, attenuates cardiac remodeling after acute myocardial infarction in the mouse. J Pharmacol Exp Ther. 2012 Dec;343(3):587-95.

[3]. Mustafa SJ, et al. 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. J Pharmacol Exp Ther. 2007 Mar;320(3):1246-51.

Chemical & Physical Properties

[ Density]:
1.44

[ Boiling Point ]:
538.4ºC at 760 mmHg

[ Molecular Formula ]:
C₂₁H₂₁F₃N₆O₂

[ Molecular Weight ]:
446.42600

[ Exact Mass ]:
446.16800

[ PSA ]:
90.50000

[ LogP ]:
3.24680

[ Index of Refraction ]:
1.64

[ Storage condition ]:
-20°C

Synthetic Route

Click to get detail synthetic route

Related Compounds

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