Design and synthesis of benzoxazole derivatives as novel melatoninergic ligands

A novel series of benzoxazole derivatives was synthesized and evaluated as melatoninergic ligands. The binding affinity of these compounds for human MT1 and MT2 receptors was determined using 2-[I-125]-iodomelatonin as the radioligand. The results of the SAR studies in this series led to the identification of compound 28, which exhibited better MT1 and MT2 receptor affinities than melatonin itself. This work also established the benzoxazole nucleus as a melatoninergic pharmacophore, which served as an isosteric replacement to the previously established alkoxyaryl core. (C) 2003 Elsevier Ltd. All rights reserved.