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In mammals,serotonin(5-hydroxytryptamine,5-HT) is a crucial neurotransmitter and plays various roles on normal physiological functions and behaviors.5-HT7 receptor is believed to be involved in regulating sleep,circadian rhythms,and the overall mood of an individual.In order to further study the potential of 5-HT7 receptors as drug targets,novel ligands with high binding affinity and selectivity for 5-HT7 receptors are sought.A series of 8-phenylisoquinoline derivatives was designed and synthesized starting from the commercially available vanillin in moderate yields.The 5-HT7 receptor binding affinities of these novel compounds were determined.The structure-activity relationship of this study provided useful information for further development of 5-HT7 receptor ligands as potential therapeutic agents to treat depression and other 5-HT7 receptor-related diseases/disorders.