Abstract

A series of 2-thiohydantoins were prepared as somatostatin subtype 4 (sst4) ligands. Reaction of a Nsubstituted- L-tryptophan methyl ester with an isothiocyanate in the presence of triethylamine readily afforded the target compounds. The 2-thiohydantoins were evaluated for binding affinities in cell lines expressing somatostatin receptor subtypes 2A (sst2A) and 4 (sst4). Compared to the thiourea NNC-26-9100 (3), all 2-thiohydantoins demonstrated lower binding affinities at sst4. Incorporation of the thiourea moiety into the more rigid 2-thiohydantoin nucleus leads to a loss of conformational freedom and may prevent optimal interaction with sst4.

Keywords: 2-Thiohydantoins, Somatostatin, Isothiocyanates, L-tryptophan methyl ester, Somatostatin receptors, Binding affinity, thiourea, triethylamine, SRIF, gastrointestinal tract, neuromodulator, structurally-related receptors , triethylamine, G-protein-coupled superfamily