The present disclosure provides substituted pyrimidine compounds of Formula I: and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein A 1 , X, A 2 , W 1 , W 2 , W 3 , E, Z, and R 4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.
