GW842166X (GW-842166X; GW842166; GW 842166X) is a novel, potent and highly selective agonist of cannabinoid receptor CB2 receptor with potential anti-inflammatory activity. It has the ability to treat inflammatory pain and activates CB2 at an EC50 of 63 nM.

Physicochemical Properties

Molecular Formula	C18H17CL2F3N4O2
Molecular Weight	449.25
Exact Mass	448.068
Elemental Analysis	C, 48.12; H, 3.81; Cl, 15.78; F, 12.69; N, 12.47; O, 7.12
CAS #	666260-75-9
Related CAS #	666260-75-9
PubChem CID	10253143
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.571
LogP	3.48
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	552
Defined Atom Stereocenter Count	0
SMILES	ClC1=CC(Cl)=C(NC2=NC=C(C(NCC3CCOCC3)=O)C(C(F)(F)F)=N2)C=C1
InChi Key	TWQYWUXBZHPIIV-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H17Cl2F3N4O2/c19-11-1-2-14(13(20)7-11)26-17-25-9-12(15(27-17)18(21,22)23)16(28)24-8-10-3-5-29-6-4-10/h1-2,7,9-10H,3-6,8H2,(H,24,28)(H,25,26,27)
Chemical Name	2-(2,4-dichloroanilino)-N-(oxan-4-ylmethyl)-4-(trifluoromethyl)pyrimidine-5-carboxamide
Synonyms	GW842166X; GW842166; GW 842166X; GW 842166; GW-842166X; 842166X; 842166; GW-842166
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	human CB2 ( IC50 = 63 nM ); rat CB2 ( IC50 = 91 nM )
ln Vitro	In vitro activity: GW842166X demonstrates comparable effectiveness and potency for rat and human recombinant CB2 receptors. In rat and human CB1 recombinant assays, it exhibits no discernible agonist activity at concentrations up to 30 µM[1].
ln Vivo	GW842166X has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain, and at 0.3 mg/kg, it completely reverses the hyperalgesic response. One hour after dosing, the blood concentrations of GW842166X in the experiments are 30 nM (0.03 mg/kg), 130 nM (0.1 mg/kg), and 370 nM (0.3 mg/kg). No statistically significant difference in the antihyperalgesic response is seen on day 4 compared to day 1 in the FCA model after 4 days of dosing, suggesting that tolerance does not develop[1].
Animal Protocol	Dissolved in saline; 15 mg/kg; p.o. administration once daily for 8 days Rat model of neuropathic pain
References	[1]. Discovery of 2-[(2,4-dichlorophenyl)amino]-N-[(tetrahydro- 2H-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a selective CB2 receptor agonist for the treatment of inflammatory pain. J Med Chem. 2007 May 31;50(11):2597-6.
Additional Infomation	5-pyrimidinecarboxamide, 2-[(2,4-dichlorophenyl)amino]-n-[(tetrahydro-2h-pyran-4-yl)methyl]-4-(trifluoromethyl)- is a dichlorobenzene. GW842166X has been used in trials studying the treatment of Pain, Analgesia, Inflammation, Osteoarthritis, and Pain, Inflammatory, among others.

Solubility Data

Solubility (In Vitro)

DMSO: ~20 mg/mL (~44.5 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.56 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 30% Propylene glycol , 5% Tween 80 , 65% D5W: 30 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2259 mL	11.1297 mL	22.2593 mL
	5 mM	0.4452 mL	2.2259 mL	4.4519 mL
	10 mM	0.2226 mL	1.1130 mL	2.2259 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.