JNJ-10397049 is a novel, potent, selective and orally bioavailable antagonist of OX2 receptor with pIC50 of 7.4 for chimeric OX2 receptors, pKB values of 5.9 and 8.5 for OX1 and OX2 receptors respectively. In a panel of more than 50 other neurotransmitters and neuropeptide receptors, it exhibits no discernible activity. It can produce a high degree of OX2 receptor occupancy in the rat brain and show signs of promoting slumber in rats. JNJ-10397049 is a substance that, when given subcutaneously to rats, prolongs and reduces the latency to persistent sleep. In rat brains examined by functional magnetic resonance imaging, this substance results in a broad attenuation of the relative cerebrovascular signal induced by D-amphetamine, with significant cortical involvement.

Physicochemical Properties

Molecular Formula	C19H20BR2N2O3
Molecular Weight	484.18
Exact Mass	481.984
Elemental Analysis	C, 47.13; H, 4.16; Br, 33.01; N, 5.79; O, 9.91
CAS #	708275-58-5
Related CAS #	708275-58-5
PubChem CID	9869934
Appearance	White to off-white solid powder
Density	1.6±0.1 g/cm3
Boiling Point	521.1±50.0 °C at 760 mmHg
Flash Point	268.9±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.647
LogP	5.66
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	485
Defined Atom Stereocenter Count	2
SMILES	CC1(OC[C@H](NC(NC2=C(Br)C=C(Br)C=C2)=O)[C@@H](O1)C3=CC=CC=C3)C
InChi Key	RBKIJGLHFFQHBE-IRXDYDNUSA-N
InChi Code	InChI=1S/C19H20Br2N2O3/c1-19(2)25-11-16(17(26-19)12-6-4-3-5-7-12)23-18(24)22-15-9-8-13(20)10-14(15)21/h3-10,16-17H,11H2,1-2H3,(H2,22,23,24)/t16-,17-/m0/s1
Chemical Name	1-(2,4-dibromophenyl)-3-[(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl]urea
Synonyms	JNJ 10397049; JNJ-10397049; JNJ10397049
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

ln Vivo	JNJ-10397049 (10–30 mg/kg) lengthens the duration of nonrapid and rapid eye movement sleep and reduces the latency for persistent sleep[2]. JNJ-10397049 inhibits reinstatement, place preference, and self-administration of ethanol[3].
Animal Protocol	Male Sprague-Dawley rats 10 mg/kg Subcutaneous administration.
References	[1]. Novel substituted 4-phenyl-[1,3]dioxanes: potent and selective orexin receptor 2 (OX(2)R) antagonists. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4225-9. [2]. Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat. J Pharmacol Exp Ther. 2009 Jul;330(1):142-51. [3]. Chimeric, mutant orexin receptors show key interactions between orexin receptors, peptides and antagonists. Eur J Pharmacol. 2011 Sep 30;667(1-3):120-8.

Solubility Data

Solubility (In Vitro)

DMSO: ~170 mg/mL (~351.1 mM) Water: N/A Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: 4.25 mg/mL (8.78 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 42.5 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: ≥ 4.25 mg/mL (8.78 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 42.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0653 mL	10.3267 mL	20.6535 mL
	5 mM	0.4131 mL	2.0653 mL	4.1307 mL
	10 mM	0.2065 mL	1.0327 mL	2.0653 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.