Design and synthesis of a novel 3-hydroxy-cyclobut-3-ene-1, 2-dione derivatives are reported and their in vitro thyroid hormone receptor selectivity has been evaluated in the thyroid luciferase receptor assay. The 3-[3, 5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)- phenylamino]-4-hydroxy-cyclobut-3-ene-1, 2-dione 21 has shown selectivity towards thyroid hormone receptor β.