Tozadenant (formerly RO-4494351; SYN-115) is an orally bioavailable, selective adenosine A2A receptor antagonist with potential usefulness in the treatment of Parkinson disease (PD). It inhibits A2A receptor with Ki of 11.5 nM on human A2A and 6 nM on rhesus A2A. It enhances motor function in Parkinson's disease animal models. Antagonists of the adenosine A(2a) receptor lessen the severity of symptoms in animal models and people with Parkinson's disease (PD). The theory that A(2a) antagonists provide this benefit by lowering the basal ganglia indirect pathway's inhibitory output is supported by research on rodents.

Physicochemical Properties

Molecular Formula	C19H26N4O4S
Molecular Weight	406.4991
Exact Mass	406.167
Elemental Analysis	C, 56.14; H, 6.45; N, 13.78; O, 15.74; S, 7.89
CAS #	870070-55-6
PubChem CID	11618368
Appearance	Solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.662
LogP	0.43
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	28
Complexity	554
Defined Atom Stereocenter Count	0
SMILES	O=C(N1CCC(C)(O)CC1)NC1SC2C(=C(C=CC=2N2CCOCC2)OC)N=1
InChi Key	XNBRWUQWSKXMPW-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H26N4O4S/c1-19(25)5-7-23(8-6-19)18(24)21-17-20-15-14(26-2)4-3-13(16(15)28-17)22-9-11-27-12-10-22/h3-4,25H,5-12H2,1-2H3,(H,20,21,24)
Chemical Name	4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)-4-methylpiperidine-1-carboxamide
Synonyms	RO 4494351; SYN 115; RO-4494351; SYN115; RO4494351; RO4494351-002; SYN-115; RO4494351-000
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

Targets	Rhesus A2A ( Ki = 6 nM ); Human A2A ( Ki = 11.5 nM )
ln Vivo	In line with the distribution of A2A receptors in the brain, 18F-MNI-444 exhibits regional uptake. Tozadenant (1.5, 10.5 mg/kg) and preladenant’s dose-dependent blocking show selectivity[1].
ADME/Pharmacokinetics	Biological Half-Life Following the oral administration of 240mg of tozadenant in healthy subjects, the mean plasma half-life was 15 hours.
References	[1]. Adenosine 2A Receptor Occupancy by Tozadenant and Preladenant in Rhesus Monkeys. J Nucl Med. 2014 Oct;55(10):1712-8.
Additional Infomation	Tozadenant is a member of benzothiazoles. Tozadenant has been investigated for the basic science of Cocaine Dependence.

Solubility Data

Solubility (In Vitro)

DMSO: ~50 mg/mL (~123.0 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 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: ≥ 2.5 mg/mL (6.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.15 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 25.0 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	2.4600 mL	12.3001 mL	24.6002 mL
	5 mM	0.4920 mL	2.4600 mL	4.9200 mL
	10 mM	0.2460 mL	1.2300 mL	2.4600 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.