| Identification | Back Directory | [Name]
Vipadenant | [CAS]
442908-10-3 | [Synonyms]
V 2006
BIIB 014
CEB 4520
VER 11135
Vipadenant
VER-ADO 49
VER-A 00049
VER-A 00-11
Vipadenant(BIIB 014)
5-BROMO-4-(METHYLSULFANYL)-1H-PYRROLO[2,3-B]PYRIDINE
3-[(4-Amino-3-methylphenyl)methyl]-7-(2-furanyl)-3H-1,2,3-triazolo[4,5-d]pyrimidin-5-amine | [Molecular Formula]
C16H15N7O | [MDL Number]
MFCD12024697 | [MOL File]
442908-10-3.mol | [Molecular Weight]
321.34 |
| Chemical Properties | Back Directory | [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 |
| Questions And Answer | Back Directory | [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
|
| Hazard Information | Back Directory | [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]
Vipadenant (0.3-30 mg/kg) produces a dose-dependent reduction in catalepsy. Vipadenant (10 mg/kg) does not produce any statistically significant dyskinetic episodes in 6-OHDA-lesioned rats during a 19-day dosing regimen[1]. In the mouse and rat haloperidol-induced hypolocomotion models, vipadenant has a minimum effective dose of 0.1 and 1 mg/kg, respectively. Vipadenant (3 and 10 mg/kg, p.o.) is able to increase contralateral rotations in 6-OHDA lesioned rats[2]. |
|
|