1 research outputs found
Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure–Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism
By reducing the basicity of the core
heterocycle in a series of
HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then
systematically explored in order to increase solubility and enable
dose escalation while retaining potency. During this exploration,
a facile decarboxylation was noted and was exploited as a novel prodrug
mechanism. The synthesis and characterization of these prodrugs and
their utilization in chronic toxicity studies are presented