Synthesis of 2-Thiohydantoins as Somatostatin Subtype 4 Receptor Ligands
A. Michael Crider.
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
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