Design and synthesis of benzoxazole derivatives as novel melatoninergic ligands

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 5; pp. 1197 - 1200
• Main Authors: SUN, Li-Qiang, JIE CHEN, TAKAKI, Katherine, JOHNSON, Graham, IBEN, Lawrence, MAHLE, Cathy D, RYAN, Elaine, XU, Cen
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 08.03.2004
• Subjects: Benzoxazoles - chemical synthesis; Benzoxazoles - metabolism; Biological and medical sciences; Drug Design; Humans; Ligands; Medical sciences; Melatonin - chemistry; Melatonin - metabolism; Melatonin - physiology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Protein Binding; Receptors, Melatonin - physiology; Human; Cyclopropane derivatives; Aliphatic compound; Ligand; In vitro; Biological fixation; Structure activity relation; Bicyclic compound; Affinity; Carboxamide; Aromatic compound; MT2 melatonin receptor; MT1 melatonin receptor; Chemical synthesis; Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.12.052

A novel series of benzoxazole derivatives was synthesized and evaluated as melatoninergic ligands. The binding affinity of these compounds for human MT(1) and MT(2) receptors was determined using 2-[(125)I]-iodomelatonin as the radioligand. The results of the SAR studies in this series led to the identification of compound 28, which exhibited better MT(1) and MT(2) 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.