Fluzoparib Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Fuzuloparib is mainly used to treat patients with recurrent ovarian, fallopian tube or primary peritoneal cancer that is sensitive to platinum-based drugs, especially those with germline breast cancer oncogene (BRCA) mutations. Tumor cells with BRCA mutations are particularly sensitive to PARP inhibitors due to defects in the homologous recombination (HR) repair pathway.
Mechanism of action
Fuzuloparib is an orally active poly(ADP-ribose) polymerase (PARP) inhibitor. PARP plays an important role in the cell's DNA damage response (DDR) and promotes the recruitment of DNA repair mechanisms by catalyzing PARylation. Fuzuloparib inhibits the function of PARP, leading to the accumulation of DNA double-strand breaks (DSBs) in tumor cells, ultimately achieving synthetic lethality.
Synthese
The synthesis started with 2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrazole, which was first reduced to the tetrahydropyrazole and then converted to the hydrochloride salt 26.2. Fuzuloparib (26) was prepared by HATU-mediated amidation of 26.2 with benzoic acid 26.3 in 88% yield.
Fluzoparib Upstream-Materialien And Downstream Produkte
Upstream-Materialien
2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)Methyl)benzoic acid
5-Bromo-2-fluorobenzoic acid
2-(TRIFLUOROMETHYL)-[1,2,4]TRIAZOLO[1,5-A]PYRAZINE
2-(TRIFLUOROMETHYL)-5,6,7,8-TETRAHYDRO-[1,2,4]TRIAZOLO[1,5-A]PYRAZINE
Downstream Produkte