Having successfully obtained new CCK1 ligands holding appropriate groups on the anthranilic acid dimer used as
molecular scaffold we were interested in increasing their micromolar affinity for the CCK1 receptors by modifying the spatial relationship
of the main pharmacophoric groups. Since, we have proposed simplified analogues reducing the anthranilic acid dimer to a
monomer. In this stage of our research program we have prepared and tested on CCK receptors a series of N-substituted anthranilic
acid derivatives keeping a Phe residue at the C-terminal site. The indole-2-carbonyl group imparts the best CCK1 receptor
binding affinity (compound 1: IC50=197.5 nM) while a sharpdecrease in binding affinity is observed for the other indole containing
derivatives. Moreover, in order to support the different binding behaviour observed for the synthesized compounds, a conformational
investigation was carried out. Finally, on the basis of the main pharmacophoric groups of the obtained new lead compound
(1) (coded VL-0395) a receptor binding hypothesis has been provided.
