Sobetirome is one of the most studied thyroid hormone receptor β (TRβ)‐selective thyromimetics in the field due to its excellent selectivity and potency. A small structural change—replacing the 3,5‐dimethyl groups of sobetirome with either chlorine or bromine—produces significantly more potent compounds, both in vitro and in vivo. These halogenated compounds induce transactivation of a TRβ‐mediated cell‐based reporter with an EC₅₀ value comparable to that of T3, access the central nervous system (CNS) at levels similar to their parent, and activate an endogenous TR‐regulated gene in the brain with an EC₅₀ value roughly five‐fold lower than that of sobetirome. Previous studies suggest that this apparent increase in affinity can be explained by halogen bonding between the ligand and a backbone carbonyl group in the receptor. This makes the new analogues potential candidates for treating CNS disorders that may respond favorably to thyroid‐hormone‐stimulated pathways.