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
Letters in Drug Design & Discovery
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:
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.
Export Options
About this article
Cite this article as:
Wang Xin, Mealer David, Rodgers Lacey, Sandoval Karin, Witt Ken, Stidsen Carsten, Ankersen Michael and Michael Crider A., Synthesis of 2-Thiohydantoins as Somatostatin Subtype 4 Receptor Ligands, Letters in Drug Design & Discovery 2012; 9 (7) . https://dx.doi.org/10.2174/157018012801319445
DOI https://dx.doi.org/10.2174/157018012801319445 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Bispidine as a Privileged Scaffold
Current Topics in Medicinal Chemistry New Tubulin Polymerization Inhibitor Derived from Thalidomide: Implications for Anti-Myeloma Therapy
Current Medicinal Chemistry Zein-Based Nanofibres for Drug Delivery: Classes and Current Applications
Current Pharmaceutical Design Dissecting Virus-Plant Interactions Through Proteomics Approaches
Current Proteomics Perinatal Brain Injury
Current Pediatric Reviews LRRC4 Inhibits Glioma Cell Growth and Invasion Through a miR-185- Dependent Pathway
Current Cancer Drug Targets Allergen-Specific Responses of CD19high and CD19low B Cells in Non-IgEMediated Food Allergy of Late Eczematous Reactions in Atopic Dermatitis: Presence of IL-17- and IL-32-Producing Regulatory B Cells (Br17 & Br32)
Inflammation & Allergy - Drug Targets (Discontinued) Non-Denaturing Solubilization of Inclusion Bodies
Current Pharmaceutical Biotechnology L-Cysteine Catalyzed Environmentally Benign One-pot Multicomponent Approach Towards the Synthesis of Dihydropyrano[2,3-c]pyrazole Derivatives
Current Organic Synthesis Anti-adhesion Molecules in IBD: Does Gut Selectivity Really Make the Difference?
Current Pharmaceutical Design The Anticancer Face of Interferon Alpha (IFN-Alpha): From Biology to Clinical Results, with a Focus on Melanoma
Current Medicinal Chemistry Novel Targets for Antiinflammatory and Antiarthritic Agents
Current Pharmaceutical Design Protein Kinase C-theta Inhibitors: A Novel Therapy for Inflammatory Disorders
Current Pharmaceutical Design Atherosclerosis and its Acute Consequences: Insights from Genetic Association Studies
Current Genomics Hypertension and Endothelial Dysfunction: Therapeutic Approach
Current Vascular Pharmacology Reversal of Bone Cancer Pain by HSV-1-Mediated Silencing of CNTF in an Afferent Area of the Spinal Cord Associated with AKT-ERK Signal Inhibition
Current Gene Therapy A Systems Biology Consideration of the Vasculopathy of Sickle Cell Anemia: The Need for Multi-Modality Chemo-Prophylaxis
Cardiovascular & Hematological Disorders-Drug Targets Immunotherapy in Invasive Fungal Infection - Focus on Invasive Aspergillosis
Current Pharmaceutical Design Nutritional Control, Gene Regulation, and Transformation of Vascular Smooth Muscle Cells in Atherosclerosis
Cardiovascular & Hematological Disorders-Drug Targets Neuroprotection in Hypoxic-Ischemic Brain Injury Targeting Glial Cells
Current Pharmaceutical Design