Synthesis and pharmacology of isoquinuclidine derivatives as 5-HT3 ligands

A series of 4-amino-5-chloro-2-methoxybenzoates and benzamides containing the 5- and 6-isoquinuclidinyl system was synthesised and evaluated for binding to 5-HT3, 5-HT4 and D2 receptors. In general, the isoquinuclidine derivatives at the 5-position have shown to be more potent as 5-HT3 ligands but they also possess 5-HT4 and D2 properties. However, the results show that the derivatives at the 6-position afforded the most promising compounds in terms of both receptor affinity and selectivity.