Vipadenant Chemical Properties

Melting point:

245.3-246.1 °C

Boiling point:

668.5±65.0 °C(Predicted)

Density 

1.56±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:37.0(Max Conc. mg/mL);115.14(Max Conc. mM)

form 

A crystalline solid

pka

4.27±0.30(Predicted)

color 

Light yellow to yellow

InChI

InChI=1S/C16H15N7O/c1-9-7-10(4-5-11(9)17)8-23-15-14(21-22-23)13(19-16(18)20-15)12-3-2-6-24-12/h2-7H,8,17H2,1H3,(H2,18,19,20)

InChIKey

HQSBCDPYXDGTCL-UHFFFAOYSA-N

SMILES

C1(N)=NC(C2=CC=CO2)=C2N=NN(CC3=CC=C(N)C(C)=C3)C2=N1

Vipadenant Usage And Synthesis

Description

Vipadenant (also known as BIIB014) is a potent, selective oral adenosine A2A receptor antagonist under development for the treatment of Parkinson’s disease. It has successfully completed phase I clinical studies. It might also be a potential adjunctive therapy reagent for cancer treatment. It was found that it has certain potentials to disrupt an immunosuppressive mechanism of tumour protection, generating improved efficacy for immunotherapies of certain cancers when used in combination with other drugs.

References

http://www.medkoo.com/products/8047
Shook, B. C., and P. F. Jackson. "Adenosine A(2A) Receptor Antagonists and Parkinson's Disease. " Acs Chemical Neuroscience2.10(2011):555-67.
Brooks, D. J., et al. "An open-label, positron emission tomography study to assess adenosine A2A brain receptor occupancy of vipadenant (BIIB014) at steady-state levels in healthy male volunteers." Clinical Neuropharmacology 33.2(2010):55.
http://www.vernalis.com/nce-pipeline/oncology/v2006

Uses

Vipadenant is a potent, selective and orally available adenosine A2A receptor antagonist under development for for Parkinson''s disease. Vipadenant demonstrates strong oral activity in commonly used models of Parkinson''s disease. Vipadenant has shown excellent preclinical pharmacokinetics and has successfully completed phase I clinical studies.

Synthesis

Example 4: Preparation of 3-(4-amino-3-methylbenzyl)-7-(furan-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine (1) To a 250 mL two-necked round-bottomed flask under nitrogen protection was added 7-(furan-2-yl)-3-(3-methyl-4-nitrobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine (3.0 g, 8.5 mmol) and 5% Pd/C catalyst (0.46 g, 0.073 mmol). Subsequently, THF (72 mL) and triethylamine (9.0 mL, 65 mmol) were added via syringe and the mixture was stirred to form a slurry. Formic acid (2.3 mL, 46.03 mmol) was then added all at once and the reaction mixture was heated in a 70 °C oil bath. After 5 hours of reaction, it was cooled to 25°C. Water (60 mL) was added and concentrated hydrochloric acid was added dropwise until the product was completely dissolved. The reaction solution was filtered through Celite 545 to remove the catalyst and the filter cake was washed with additional water (2 x 5 mL). A 50% aqueous sodium hydroxide solution was added to the pale yellow filtrate to precipitate the product. After continued stirring for 1 hour, the product was separated by filtration. The filter cake was washed sequentially with water (10 mL) and methanol (10 mL). The product was dried under vacuum to constant weight to give 2.79 g (92% yield) of the target compound 3-(4-amino-3-methylbenzyl)-7-(furan-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine.

in vivo

References

[1] Patent: WO2008/86201, 2008, A1. Location in patent: Page/Page column 21
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 1, p. 33 - 47

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