Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists

The structure‐activity relationship optimization of the pyrazoline template 3a resulted in novel 3‐oxo‐1,2‐diphenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐indole carboxamides 4a–4e. These non‐peptidal CCK ligands have been shown to act as potent CCK1 ligands in a [125]I‐CCK‐8 receptor binding assay. The best amides (4c and 4d) of this series displayed an IC50 of 20/25 nm for the CCK1 receptor. In a subsequent in‐vivo evaluation using various behaviour pharmacological assays, an anxiolytic effect of these novel 3‐oxo‐1,2‐diphenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐indole carboxamides was found at high doses in the elevated plus‐maze. In the despair swimming test, a model for testing antidepressants, an ED50 of 0.33/0.41 mg kg−1 was determined for amide 4c/4d and the antidepressant effect had a magnitude comparable to desimipramine.