GW-405,833

GW-405,833

Identifiers
IUPAC name 1-(2,3-Dichlorobenzoyl)-5-methoxy-2-methyl-3-[2-(4-morpholinyl)ethyl]-1H-indole
CAS Number	180002-83-9
PubChem (CID)	9911463
ChemSpider	8087114
ChEMBL	CHEMBL73711
ECHA InfoCard	100.162.054
Chemical and physical data
Formula	C23H24Cl2N2O3
Molar mass	447.353 g/mol
3D model (Jmol)	Interactive image
SMILES CC1=C(C2=C(N1C(=O)C3=C(C(=CC=C3)Cl)Cl)C=CC(=C2)OC)CCN4CCOCC4 C4COCCN4CCc1c(C)n(c(ccc3OC)c1c3)C(=O)c2cccc(Cl)c2Cl
InChI InChI=1S/C23H24Cl2N2O3/c1-15-17(8-9-26-10-12-30-13-11-26)19-14-16(29-2)6-7-21(19)27(15)23(28)18-4-3-5-20(24)22(18)25/h3-7,14H,8-13H2,1-2H3 Key:FSFZRNZSZYDVLI-UHFFFAOYSA-N
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GW-405,833 (L-768,242) is a drug that acts as a potent and selective partial agonist for the cannabinoid receptor subtype CB₂, with an EC₅₀ of 0.65 nM and selectivity of around 1200x for CB₂ over CB₁ receptors.^[1][2] Animal studies have shown it to possess antiinflammatory and anti-hyperalgesic effects at low doses, followed by ataxia and analgesic effects when the dose is increased.^[3][4] Selective CB₂ agonist drugs such as GW-405,833 are hoped to be particularly useful in the treatment of allodynia and neuropathic pain for which current treatment options are often inadequate.^[5][6]

References

1. Huffman JW. The search for selective ligands for the CB2 receptor. Current Pharmaceutical Design. 2000 Sep;6(13):1323-37. doi:10.2174/1381612003399347 PMID 10903395
2. Marriott KS, Huffman JW. Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor. Current Topics in Medicinal Chemistry. 2008;8(3):187-204. doi:10.2174/156802608783498014 PMID 18289088
3. Clayton N, Marshall FH, Bountra C, O'Shaughnessy CT. CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain. 2002 Apr;96(3):253-60. PMID 11972997
4. Valenzano KJ, Tafesse L, Lee G, Harrison JE, Boulet JM, Gottshall SL, Mark L, Pearson MS, Miller W, Shan S, Rabadi L, Rotshteyn Y, Chaffer SM, Turchin PI, Elsemore DA, Toth M, Koetzner L, Whiteside GT. Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacology. 2005 Apr;48(5):658-72. PMID 15814101
5. Beltramo M, Bernardini N, Bertorelli R, Campanella M, Nicolussi E, Fredduzzi S, Reggiani A. CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. European Journal of Neuroscience. 2006 Mar;23(6):1530-8. doi:10.1111/j.1460-9568.2006.04684.x PMID 16553616
6. Leichsenring A, Andriske M, Bäcker I, Stichel CC, Lübbert H. Analgesic and antiinflammatory effects of cannabinoid receptor agonists in a rat model of neuropathic pain. Naunyn Schmiedebergs Archives of Pharmacology. 2009 Jan 18. PMID 19152053