SB-649868 (original) (raw)

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Chemical compound

SB-649868
Clinical data
ATC code None
Legal status
Legal status Investigational
Identifiers
IUPAC name N_-([(2_S)-1-([5-(4-fluorophenyl)-2-methyl-4-thiazolyl]carbonyl)-2-piperidinyl]methyl)-4-benzofurancarboxamide
CAS Number 380899-24-1 checkY
PubChem CID 25195495
ChemSpider 25069706
UNII 1L1V1K2M4V
ChEMBL ChEMBL1272307
CompTox Dashboard (EPA) DTXSID90191491 Edit this at Wikidata
Chemical and physical data
Formula C26H24FN3O3S
Molar mass 477.55 g·mol−1
3D model (JSmol) Interactive image
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/s1Key:ZJXIUGNEAIHSBI-IBGZPJMESA-N

SB-649868 is a dual orexin receptor antagonist that was being developed by GlaxoSmithKline as a treatment for insomnia.[1]

A phase I clinical trial 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 phase II study added a 60 mg dose and observed dose-dependent sleep promotion.[4]

The compound no longer appears to be under active development, with the last study posted to ClinicalTrials.gov completed in 2010.

  1. ^ Renzulli C, Nash M, Wright M, Thomas S, Zamuner S, Pellegatti M, et al. (February 2011). "Disposition and metabolism of [14C]SB-649868, an orexin 1 and 2 receptor antagonist, in humans". Drug Metabolism and Disposition. 39 (2): 215–27. doi:10.1124/dmd.110.035386. PMID 21045199. S2CID 1995624.
  2. ^ Bettica P, Nucci G, Pyke C, Squassante L, Zamuner S, Ratti E, et al. (August 2012). "Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist". Journal of Psychopharmacology. 26 (8): 1058–70. doi:10.1177/0269881111408954. PMID 21730017. S2CID 29578953.
  3. ^ Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk DJ (April 2012). "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 (5): 1224–33. doi:10.1038/npp.2011.310. PMC 3306884. PMID 22237311.
  4. ^ Bettica P, Squassante L, Zamuner S, Nucci G, Danker-Hopfe H, Ratti E (August 2012). "The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia". Sleep. 35 (8): 1097–104. doi:10.5665/sleep.1996. PMC 3397789. PMID 22851805.