Novel selective human melanocortin-3 receptor ligands: use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold
| Autor: | Dagmara Tymecka, Minying Cai, Alexander V. Mayorov, Aleksandra Misicka, Steven Ballet, Dirk Tourwé, Karolien Van Rompaey, Erin S. Palmer, Kevin B. Chandler, Victor J. Hruby |
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| Rok vydání: | 2007 |
| Předmět: |
Agonist
Magnetic Resonance Spectroscopy Stereochemistry medicine.drug_class Chemistry Pharmaceutical Clinical Biochemistry Molecular Conformation Pharmaceutical Science Ligands Biochemistry Article Inhibitory Concentration 50 Melanocortin receptor Drug Discovery medicine Humans Receptor Molecular Biology G protein-coupled receptor Bicyclic molecule Chemistry Receptors Melanocortin Organic Chemistry Antagonist Benzazepines Melanocortin 3 receptor Models Chemical Receptors Corticotropin Drug Design Molecular Medicine Melanocortin Peptides Receptor Melanocortin Type 3 |
| Zdroj: | Bioorganicmedicinal chemistry letters. 17(9) |
| ISSN: | 0960-894X |
| Popis: | In search of new selective antagonists and/or agonists for the human melanocortin receptor subtypes hMC1R to hMC5R to elucidate the specific biological roles of each GPCR, we modified the structures of the superagonist MT-II (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH(2)) and the hMC3R/hMC4R antagonist SHU9119 (Ac-Nle-c[Asp-His-D-Nal(2')-Arg-Trp-Lys]-NH(2)) by replacing the His-d-Phe and His-d-Nal(2') fragments in MT-II and SHU9119, respectively, with Aba-Xxx (4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one-Xxx) dipeptidomimetics (Xxx=D-Phe/pCl-D-Phe/D-Nal(2')). Employment of the Aba mimetic yielded novel selective high affinity hMC3R and hMC3R/hMC5R antagonists. |
| Databáze: | OpenAIRE |
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