Bioactivity-guided synthesis of tropine derivatives as new agonists for melatonin receptors†
Abstract
Twenty-three tropine derivatives as new melatonin receptor (MT1 and MT2) agonists were synthesized and evaluated on HEK293 cells in vitro. Derivatives 1f, 1i, 1j, 1m–1s and 1t exhibited increased agonisting activities on MT1 and MT2 receptors compared to the substrate tropine. Particularly, compound 1r showed significant agonistic activities on MT1 and MT2 receptors with EC50 values of 0.20 and 0.24 mM, respectively. The preliminary structure–activity relationships (SARs) of tropine derivatives were summarized for further investigation on melatonin receptor agonists.