Tivozanib Chemische Eigenschaften,Einsatz,Produktion Methoden
Charakteristisch
Primary targets: VEGFR/multikinase
Class: receptor tyrosine kinase
Treatment: RCC
Elimination half-life = 111 h
Protein binding = >99%
Verwenden
Tivozanib also known as AV-951 is an orally bioavailable potent VEGFR-1, 2 and 3, c-Kit and PDGFR inhibitor with IC50 of 0.21, 0.16, 0.24, 1.63 and 1.72 nM, respectively.
Synthese
The synthesis of Tivozanib is as follows:
Phenyl chlorocarbonate (601 g) was added dropwise to 3-amino-5-methylisoxazole (377 g), pyridine (1215 g), and N,N-dimethylacetamide (4 L) at 0°C, and the mixture was stirred at 20°C for 2 hr. 4-[(4-Amino-3-chlorophenol)oxy]-6,7-dimethoxyquinoline (847 g) was added to the reaction solution, and the mixture was stirred at 80°C for 5 hr. The reaction solution was cooled to 5°C. Thereafter, methanol (8.5 L) and water (8.5 L) were added thereto, and the mixture was neutralized with an aqueous sodium hydroxide solution. The resultant precipitate was collected by filtration, and the filtered product was slurried in water (8.5 L) for washing. The slurry was filtered, and the filtered product was then dried under the reduced pressure to give Tivozanib (1002 g, yield 86.1%).
Tivozanib Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
