Structural modifications of a 3-methoxy-2-aminopyridine compound to reduce potential for mutagenicity and time-dependent drug-drug interaction

Potent bRAF inhibitors containing 3-methoxy-2-aminopyridine moiety were shown to be representative examples of an electron rich heteroaryl associated with time-dependent drug-drug interactions and mutagenicity. These risks may be reduced by either reducing electron density or preventing the formation of the mutagenic metabolite.