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.