4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide Chemical Properties

Density 

1.374

storage temp. 

Store at -20°C

solubility 

insoluble in EtOH; insoluble in H2O; ≥20.35 mg/mL in DMSO

form 

Powder

pka

14.95±0.20(Predicted)

color 

White to off-white

InChI

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)

InChIKey

XNBRWUQWSKXMPW-UHFFFAOYSA-N

SMILES

N1(C(NC2=NC3=C(OC)C=CC(N4CCOCC4)=C3S2)=O)CCC(O)(C)CC1

4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide Usage And Synthesis

Description

Tozadenant is an adenosine A_2A receptor antagonist (K_is = 11.5 and 6 nM for the human and rhesus monkey receptors, respectively). It increases the distance traveled and reduces contralateral asymmetry in the open field test in a rat model of Parkinson''s disease induced by 6-OHDA when administered at a dose of 30 mg/kg. Tozadenant (150 mg/kg) reverses locomotor deficits and restores novel object-stimulated locomotion in a marmoset model of MPTP-induced Parkinson''s disease.

Uses

Tozadenant is an adenosine A2A receptor antagonist, with Ki of 11.5 nM on human A2A and 6 nM on rhesus A2A.

Definition

ChEBI: Tozadenant is a member of benzothiazoles.

Synthesis

Phenyl (4-methoxy-7-morpholin-4-ylbenzo[D]thiazol-2-yl) carbamate (3.2 g, 8.3 mmol) and 4-methyl-4-hydroxypiperidine were used as raw materials and both were dissolved in trichloromethane (50 ml) in the presence of N-ethyl diisopropylamine (4.4 ml, 25 mmol). Subsequently, a mixed solution of trichloromethane (3 ml) and tetrahydrofuran (3 ml) of 4-hydroxy-4-methylpiperidine was added to this solution. The reaction mixture was heated to reflux for 1 hour. After completion of the reaction, the mixture was cooled to room temperature and washed sequentially with saturated aqueous sodium carbonate solution (15 ml) and water (2 x 5 ml). The organic phase was dried over magnesium sulfate and the solvent was concentrated under reduced pressure, the resulting crude product was recrystallized from ethanol to afford the target compound 4-hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide as white crystals in 78% yield, melting point 236 °C. Mass spectral analysis showed m/e = 407 (M + H+).

in vivo

target

adenosine A2A receptor

References

hauser ra, olanow cw, kieburtz kd et al. tozadenant (syn115) in patients with parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. lancet neurol. 2014 aug;13(8):767-76.