Bioactivity-guided synthesis of gramine derivatives as new MT 1 and 5-HT 1A receptors agonists.

Twenty-four gramine derivatives were synthesized and evaluated on MT1and 5-HT1Areceptorsin vitro. Among them, seven derivatives (7,8,16,19,20,21,and24)exhibited higher agonisting activities on MT1or 5-HT1Areceptors. Compared with gramine, derivatives7,8,16,19,20,21,and24displayed 1.6–3.5-fold increase in agonistic rates on 5-HT1Areceptor. Particularly, derivatives7,19,and21exhibited significant agonistic activities on MT1and 5-HT1Areceptors with EC50values of 0.51, 0.39, 0.50 mΜ and 0.28, 0.46, 0.23 mΜ, respectively. The preliminary structure–activity relationships of gramine derivatives were summarized for further investigation on MT1and 5-HT1Areceptors as new potential agonists. [ABSTRACT FROM PUBLISHER]