Donafenib Chemische Eigenschaften,Einsatz,Produktion Methoden
Mechanism of action
Donafenib blocks the proliferation of tumor cells by inhibiting Raf kinase and VEGFR tyrosine kinase. The deuterated methyl group in donafenib improves the metabolic stability of the drug, resulting in a prolonged half-life, reduced systemic clearance, and increased systemic exposure. Donafenib has shown significantly improved overall survival compared to sorafenib in the treatment of patients with unresectable HCC, while having a favorable safety and tolerability profile.
Chemische Eigenschaften
Off-White to Light Pink Solid
Verwenden
Labelled Sorafenib, a potent RAF kinase inhibitor. Antineoplastic.
Synthese
The synthetic route began with the amidation of methyl formate 31.2 using chloromethane-d3-amine (31.1) as a deuterium source to afford CD3-amide 31.3 in high yield (98%). Aminophenol 31.4 was reacted with 31.2 in dimethyl sulfoxide via a SNAr displacement reaction to afford diaryl ether 31.5. Finally, aniline was reacted with isocyanate 31.6 to synthesize donafenib (31) from 31.3 in 79% yield.
Donafenib Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
