Synthesis and pharmacological activity of a macrocyclic benzamide

a macrocyclic benzamide was synthesized and its affinities for 5-HT3, 5-HT4 and D2 receptors were evaluated in binding assays. It was compared to reference benzamldes possessing a piperidine ring with varlous orlentations of the N-substituent. It was clearly demonstrated that the orientation of the basic nitrogen atom lone pair is an essential structural parameter in the recognition of 5-HT3 and 5-HT4 receptors.