Donafenib

Donafenib Property

Melting point:

202-204?C

storage temp. 

-20°C Freezer

solubility 

DMSO: soluble; Methanol: soluble

form 

A solid

color 

White to off-white

InChI

InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)

InChIKey

MLDQJTXFUGDVEO-UHFFFAOYSA-N

SMILES

c1(Cl)ccc(NC(Nc2ccc(Oc3ccnc(C(=O)NC)c3)cc2)=O)cc1C(F)(F)F

Hazard and Precautionary Statements (GHS)

Donafenib Chemical Properties,Usage,Production

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.

Chemical Properties

Off-White to Light Pink Solid

Uses

Labelled Sorafenib, a potent RAF kinase inhibitor. Antineoplastic.

Synthesis

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.