Novel small molecule neurotensin antagonists: 3-(1,5-diaryl-1,5-dioxopentan-3-yl)benzoic acids

Abstract Screening in a neurotensin (NT) receptor binding assay resulted in the discovery of compound 1 with NT receptor binding affinity of 450 nM. SAR studies that varied substituents on each aromatic ring and the linking 1,5-pentanedione chain lead to compound 39 with 42 nM affinity. The more potent compounds were shown to be NT antagonists by their ability to inhibit NT induced calcium mobilization in HT29 cells.