SB-649,868

SB-649,868

Systematic (IUPAC) name
N-([(2S)-1-([5-(4-fluorophenyl)-2-methyl-4-thiazolyl]carbonyl)-2-piperidinyl]methyl)-4-benzofurancarboxamide
Clinical data
Legal status	Investigational
Identifiers
ATC code	None
PubChem	CID 25195495
ChemSpider	25069706
ChEMBL	CHEMBL1272307
Chemical data
Formula	C26H24FN3O3S
Molar mass	477.549 g/mol (free base)
SMILES CC1=NC(=C(S1)C2=CC=C(C=C2)F)C(=O)N3CCCC[C@H]3CNC(=O)C4=C5C=COC5=CC=C4
InChI InChI=1S/C26H24FN3O3S/c1-16-29-23(24(34-16)17-8-10-18(27)11-9-17)26(32)30-13-3-2-5-19(30)15-28-25(31)21-6-4-7-22-20(21)12-14-33-22/h4,6-12,14,19H,2-3,5,13,15H2,1H3,(H,28,31)/t19-/m0/s1 Key:ZJXIUGNEAIHSBI-IBGZPJMESA-N

SB-649,868 is a dual orexin receptor antagonist in development by GlaxoSmithKline.^[1] The drug is currently in phase II development for insomnia.

A phase I study evaluated doses up to 80 mg, resulting in significant improvement in sleep latency without adverse effects.^[2]

In randomized, double-blind, placebo-controlled crossover trials, the 10 and 30 mg doses increased sleep time and reduced sleep latency.^[3] The subsequent study added a 60 mg dose and observed dose-dependent sleep promotion.^[4]

See also

• Almorexant
• Filorexant
• Lemborexant
• Suvorexant

References

1. Renzulli C, Nash M, Wright M, Thomas S, Zamuner S, Pellegatti M, Bettica P, Boyle G (February 2011). "Disposition and metabolism of [14C]SB-649868, an orexin 1 and 2 receptor antagonist, in humans" (PDF). Drug Metab. Dispos. 39 (2): 215–27. doi:10.1124/dmd.110.035386. PMID 21045199.
2. "Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist.". Journal of Psychopharmacology 26: 1058–1070. Aug 2012. doi:10.1177/0269881111408954. PMID 21730017.
3. "Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia.". Neuropsychopharmacology 37: 1224–33. Apr 2012. doi:10.1038/npp.2011.310. PMID 22237311.
4. "The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia.". Sleep 35: 1097–104. Aug 2012. doi:10.5665/sleep.1996. PMID 22851805.

Further reading

• Ratti E (December 13, 2007). "Psychiatry: An Innovative Drug Discovery Pipeline" (PDF) (GSK Neurosciences seminar). Archived from the original on December 5, 2008.
• Scammell TE, Winrow CJ (February 2011). "Orexin receptors: pharmacology and therapeutic opportunities". Annu. Rev. Pharmacol. Toxicol. 51: 243–66. doi:10.1146/annurev-pharmtox-010510-100528. PMC 3058259. PMID 21034217.