Synthesis of 2-Thiohydantoins as Somatostatin Subtype 4 Receptor Ligands

Author(s): Xin Wang, David Mealer, Lacey Rodgers, Karin Sandoval, Ken Witt, Carsten Stidsen, Michael Ankersen, A. Michael Crider

Journal Name: Letters in Drug Design & Discovery

Volume 9 , Issue 7 , 2012


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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

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Article Details

VOLUME: 9
ISSUE: 7
Year: 2012
Published on: 25 June, 2012
Page: [655 - 662]
Pages: 8
DOI: 10.2174/157018012801319445
Price: $65

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