SB649868 | CAS#380899-24-1 | Orexin receptor antagonist

MedKoo Cat#: 526934 | Name: SB649868

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SB649868, also known as GSK-649868, is an orexin receptor antagonist potentially for the treatment of insomnia and sleep disorder. SB649868 promotes and maintains sleep in men with primary insomnia. SB649868 may be a potentially effective and well-tolerated treatments for patients with sleep disorders.

Chemical Structure

SB649868

CAS#380899-24-1

Theoretical Analysis

MedKoo Cat#: 526934

Name: SB649868

CAS#: 380899-24-1

Chemical Formula: C26H24FN3O3S

Exact Mass: 477.1522

Molecular Weight: 477.55

Elemental Analysis: C, 65.39; H, 5.07; F, 3.98; N, 8.80; O, 10.05; S, 6.71

Price and Availability

Size	Price	Availability
100mg	USD 1,550.00	2 Weeks
200mg	USD 2,150.00	2 Weeks
500mg	USD 2,950.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 5,250.00	2 Weeks

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Related CAS #

No Data

Synonym

GSK-649868; GSK 649868; GSK649868; SB649868; SB-649868; SB 649868.

IUPAC/Chemical Name

(S)-N-((1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)piperidin-2-yl)methyl)benzofuran-4-carboxamide

InChi Key

ZJXIUGNEAIHSBI-IBGZPJMESA-N

InChi Code

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

SMILES Code

O=C(C1=C2C=COC2=CC=C1)NC[C@H]3N(C(C4=C(C5=CC=C(F)C=C5)SC(C)=N4)=O)CCCC3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SB649868 is an OX1 and OX2 receptor antagonist (pKi =9.4 and 9.5 at the OX1 and OX2 receptor, respectively).

In vitro activity:

SB649868 displayed specific interactions with OX1 and OX2, showing their ability to antagonize orexin-A-induced inositol 1 phosphate accumulation. SB649868 demonstrated a non-surmountable profile at the OX1 receptor. Reference: Eur J Pharmacol. 2012 Oct 5;692(1-3):1-9. https://pubmed.ncbi.nlm.nih.gov/22796453/

In vivo activity:

SB649868 had sleep-promoting properties in male patients with insomnia. SB649868 significantly reduced latency to persistent sleep, wake after sleep onset, and increased total sleep time. SB649868 was well tolerated with inconsistent next day residual effects. SB649868 sleep effects were correlated with SB649868 circulating levels. Reference: Sleep. 2012 Aug 1;35(8):1097-104. https://pubmed.ncbi.nlm.nih.gov/22851805/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	209.40

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 477.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Faedo S, Perdonà E, Antolini M, di Fabio R, Merlo Pich E, Corsi M. Functional and binding kinetic studies make a distinction between OX1 and OX2 orexin receptor antagonists. Eur J Pharmacol. 2012 Oct 5;692(1-3):1-9. doi: 10.1016/j.ejphar.2012.07.007. Epub 2012 Jul 13. PMID: 22796453. 2. Bettica P, Squassante L, Zamuner S, Nucci G, Danker-Hopfe H, Ratti E. The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep. 2012 Aug 1;35(8):1097-104. doi: 10.5665/sleep.1996. PMID: 22851805; PMCID: PMC3397789. 3. Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk DJ. 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. 2012 Apr;37(5):1224-33. doi: 10.1038/npp.2011.310. Epub 2012 Jan 11. PMID: 22237311; PMCID: PMC3306884.

In vitro protocol:

In vivo protocol:

1. Bettica P, Squassante L, Zamuner S, Nucci G, Danker-Hopfe H, Ratti E. The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep. 2012 Aug 1;35(8):1097-104. doi: 10.5665/sleep.1996. PMID: 22851805; PMCID: PMC3397789. 2. Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk DJ. 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. 2012 Apr;37(5):1224-33. doi: 10.1038/npp.2011.310. Epub 2012 Jan 11. PMID: 22237311; PMCID: PMC3306884.

1: Yun S, Wennerholm M, Shelton JE, Bonaventure P, Letavic MA, Shireman BT, Lovenberg TW, Dugovic C. Selective Inhibition of Orexin-2 Receptors Prevents Stress-Induced ACTH Release in Mice. Front Behav Neurosci. 2017 May 8;11:83. doi: 10.3389/fnbeh.2017.00083. PMID: 28533747; PMCID: PMC5420581. 2: Jacobson LH, Callander GE, Hoyer D. Suvorexant for the treatment of insomnia. Expert Rev Clin Pharmacol. 2014 Nov;7(6):711-30. doi: 10.1586/17512433.2014.966813. PMID: 25318834. 3: Boss C, Roch-Brisbare C, Steiner MA, Treiber A, Dietrich H, Jenck F, von Raumer M, Sifferlen T, Brotschi C, Heidmann B, Williams JT, Aissaoui H, Siegrist R, Gatfield J. Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain- penetrant dual orexin 1/orexin 2 receptor antagonist. ChemMedChem. 2014 Nov;9(11):2486-96. doi: 10.1002/cmdc.201402258. Epub 2014 Aug 21. PMID: 25147058. 4: Patel AX, Miller SR, Nathan PJ, Kanakaraj P, Napolitano A, Lawrence P, Koch A, Bullmore ET. Neuroendocrine and sympathetic responses to an orexin receptor antagonist, SB-649868, and alprazolam following insulin-induced hypoglycemia in humans. Psychopharmacology (Berl). 2014 Oct;231(19):3817-28. doi: 10.1007/s00213-014-3520-7. Epub 2014 Apr 26. PMID: 24770625; PMCID: PMC4159598. 5: Dugovic C, Shelton JE, Yun S, Bonaventure P, Shireman BT, Lovenberg TW. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism. Front Neurosci. 2014 Feb 14;8:28. doi: 10.3389/fnins.2014.00028. PMID: 24592208; PMCID: PMC3924048. 6: Callander GE, Olorunda M, Monna D, Schuepbach E, Langenegger D, Betschart C, Hintermann S, Behnke D, Cotesta S, Fendt M, Laue G, Ofner S, Briard E, Gee CE, Jacobson LH, Hoyer D. Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors. Front Neurosci. 2013 Dec 3;7:230. doi: 10.3389/fnins.2013.00230. PMID: 24376396; PMCID: PMC3847553. 7: Hoyer D, Dürst T, Fendt M, Jacobson LH, Betschart C, Hintermann S, Behnke D, Cotesta S, Laue G, Ofner S, Legangneux E, Gee CE. Distinct effects of IPSU and suvorexant on mouse sleep architecture. Front Neurosci. 2013 Dec 10;7:235. doi: 10.3389/fnins.2013.00235. PMID: 24368893; PMCID: PMC3857892. 8: Hoyer D, Jacobson LH. Orexin in sleep, addiction and more: is the perfect insomnia drug at hand? Neuropeptides. 2013 Dec;47(6):477-88. doi: 10.1016/j.npep.2013.10.009. Epub 2013 Oct 23. PMID: 24215799. 9: Betschart C, Hintermann S, Behnke D, Cotesta S, Fendt M, Gee CE, Jacobson LH, Laue G, Ofner S, Chaudhari V, Badiger S, Pandit C, Wagner J, Hoyer D. Identification of a novel series of orexin receptor antagonists with a distinct effect on sleep architecture for the treatment of insomnia. J Med Chem. 2013 Oct 10;56(19):7590-607. doi: 10.1021/jm4007627. Epub 2013 Sep 18. PMID: 23964859. 10: Winrow CJ, Renger JJ. Discovery and development of orexin receptor antagonists as therapeutics for insomnia. Br J Pharmacol. 2014 Jan;171(2):283-93. doi: 10.1111/bph.12261. PMID: 23731216; PMCID: PMC3904252. 11: Bettica P, Squassante L, Zamuner S, Nucci G, Danker-Hopfe H, Ratti E. The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep. 2012 Aug 1;35(8):1097-104. doi: 10.5665/sleep.1996. PMID: 22851805; PMCID: PMC3397789. 12: Faedo S, Perdonà E, Antolini M, di Fabio R, Merlo Pich E, Corsi M. Functional and binding kinetic studies make a distinction between OX1 and OX2 orexin receptor antagonists. Eur J Pharmacol. 2012 Oct 5;692(1-3):1-9. doi: 10.1016/j.ejphar.2012.07.007. Epub 2012 Jul 13. PMID: 22796453. 13: Piccoli L, Micioni Di Bonaventura MV, Cifani C, Costantini VJ, Massagrande M, Montanari D, Martinelli P, Antolini M, Ciccocioppo R, Massi M, Merlo-Pich E, Di Fabio R, Corsi M. Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats. Neuropsychopharmacology. 2012 Aug;37(9):1999-2011. doi: 10.1038/npp.2012.48. Epub 2012 May 9. PMID: 22569505; PMCID: PMC3398727. 14: Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk DJ. 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. 2012 Apr;37(5):1224-33. doi: 10.1038/npp.2011.310. Epub 2012 Jan 11. PMID: 22237311; PMCID: PMC3306884. 15: Bettica P, Nucci G, Pyke C, Squassante L, Zamuner S, Ratti E, Gomeni R, Alexander R. Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist. J Psychopharmacol. 2012 Aug;26(8):1058-70. doi: 10.1177/0269881111408954. Epub 2011 Jul 5. PMID: 21730017. 16: Renzulli C, Nash M, Wright M, Thomas S, Zamuner S, Pellegatti M, Bettica P, Boyle G. Disposition and metabolism of [14C]SB-649868, an orexin 1 and 2 receptor antagonist, in humans. Drug Metab Dispos. 2011 Feb;39(2):215-27. doi: 10.1124/dmd.110.035386. Epub 2010 Nov 2. Erratum in: Drug Metab Dispos. 2011 Jun;39(6):1111. PMID: 21045199.