Title:Synthesis of 2-Thiohydantoins as Somatostatin Subtype 4 Receptor Ligands
VOLUME: 9 ISSUE: 7
Author(s):Xin Wang, David Mealer, Lacey Rodgers, Karin Sandoval, Ken Witt, Carsten Stidsen, Michael Ankersen and A. Michael Crider
Affiliation:Department of Pharmaceutical Sciences, School of Pharmacy, Southern Illinois University Edwardsville, Edwardsville, IL 62026-2000, USA.
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
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.
