Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular 
endothelial growth factor receptor-1(VEGFR1), -2(VEGFR2), and -3(VEGFR3). Analog 
of Tivozanib with deuterium-for-hydrogen replacement in metabolically active 
site was prepared and evaluated in vitro. Compared to its prototype, deuterated 
Tivozanib compound HC-1144 retained in vitro activity against VEGFR tyrosine 
kinases. In vivo pharmacokinetic studies indicated HC-1144 clearly altered the 
blood circulation behavior, which was proved by significantly prolonged blood 
circulation half life time (t1/2) and increased AUC0-∞. Therefore, HC-1144 has 
the potential to be a novel inhibitor against VEGFR tyrosine kinases with 
long-acting plasma exposure.